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ResearchIn-Press PreviewAIDS/HIVImmunology Open Access | 10.1172/JCI192575

A favorable follicular helper CD4 T cell programming characterizes neutralization activity in chronic HIV infection

Eirini Moysi,1 Ashish A. Sharma,2 Sijy O'Dell,3 Spiros Georgakis,4 Perla Mariana Del Rio Estrada,2 Ghneim Khader,2 Alonso Arana,2 Fernanda Torres-Ruiz,5 Mauricio González Navarro,5 Yara Andrea Luna Villalobos,5 Santiago Avila Rios,5 Gustavo Reyes-Teran,6 Margaret H. Beddall,7 Sung Hee Ko,8 Frida Belinky,8 Michail Orfanakis,4 Laurence de Leval,4 Ana B. Enriquez,2 Clarisa M. Buckner,9 Susan Moir,9 Helen Lindsay,10 Raphael Gottardo,10 Nicole Doria-Rose,3 Eli A. Boritz,8 John R. Mascola,3 Rafick-Pierre Sekaly,2 Richard A. Koup,1 and Constantinos Petrovas1

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Moysi, E. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Sharma, A. in: PubMed | Google Scholar |

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by O'Dell, S. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Georgakis, S. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Del Rio Estrada, P. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Khader, G. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Arana, A. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Torres-Ruiz, F. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by González Navarro, M. in: PubMed | Google Scholar |

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Luna Villalobos, Y. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Avila Rios, S. in: PubMed | Google Scholar |

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Reyes-Teran, G. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Beddall, M. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Ko, S. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Belinky, F. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Orfanakis, M. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by de Leval, L. in: PubMed | Google Scholar |

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Enriquez, A. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Buckner, C. in: PubMed | Google Scholar

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

Find articles by Moir, S. in: PubMed | Google Scholar |

1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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1Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

2Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, United States of America

3Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

4Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

5Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

6Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico

7ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

8Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

9Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

11Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, United States of America

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Published July 14, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI192575.
Copyright © 2026, Moysi et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 14, 2026 - Version history
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Abstract

A subset of people living with HIV (PLWH) can produce broadly neutralizing antibodies (bNAbs) against HIV, but the lymph node (LN) dynamics that promote the generation of these antibodies are poorly understood. Here, we explored LN-associated histological, immunological, and virological determinants of bNAb generation in a cohort of anti-retroviral therapy (ART)-naïve PLWH. We found that participants who produce bNAbs, termed neutralizers, have a better-preserved LN-associated B cell follicle architecture compared with PLWH who do not. The former was associated with a substantially higher in situ prevalence of Bcl-6hi follicular helper CD4 T cells (TFH), expressing a molecular program that favors their differentiation and stemness, and substantially reduced IL-10 follicular suppressor CD4 T cells. Furthermore, our data reveal possible molecular targets mediating TFH- B cell interactions in neutralizers. Together, we identify germinal center cellular and molecular signatures that could contribute to the development of bNAbs in PLWH.

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