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Clinical Research and Public HealthIn-Press PreviewImmunologyVirology Open Access | 10.1172/JCI203138

HIV causes global B-cell dysregulation and restricts HBV-specific B-cell development in an incident HBV cohort

Katherine Cascino,1 Thomas Liechti,2 Eric C. Seaberg,3 Kathleen E. Stevens,1 Steven M. Wolinsky,4 Mallory D. Witt,5 Robbie B. Mailliard,6 Mario Roederer,2 Justin Bailey,1 Chloe L. Thio,1 and Andrea L. Cox1

1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America

2Vaccine Research Center, NIAID, Bethesda, United States of America

3Department of Epidemiology, Johns Hopkins University, Baltimore, United States of America

4Division of Infectious Diseases, Northwestern University, Chicago, United States of America

5Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, United States of America

6Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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Published April 7, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI203138.
Copyright © 2026, Cascino 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 April 7, 2026 - Version history
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Abstract

Background. Functional B cell responses for both prevention and control of hepatitis B virus (HBV) infection remain poorly understood, including in the context of HBV/HIV co-infection. Methods. Here, we employed high-dimensional single cell analysis to assess global and hepatitis B surface antigen (HBsAg)-specific B cells in a longitudinal cohort of incident HBV from the Multicenter Aids Cohort Study (MACS), with a subset of the cohort living with HIV-1. Results. We observed that prior HIV infection has negative consequences for B cell function in early post-acute HBV infection, including increased frequencies of atypical memory (AtM) B cells and regulatory B cells (Bregs), expression of the activation marker CD86 on multiple B cell subsets in chronic HBV (CHB), and restricted expansion of HBsAg-specific B cells. In contrast, in HBV mono-infection, we observed no changes in the global B cell population from prior to infection and robust expansion of HBsAg-specific B cells. These expanded antigen-specific B cells resembled class-switched intermediate and resting memory (IM and RM) B cells, with activation phenotypes that may contribute to ongoing HBV control. Conclusion. HIV infection has a significant impact on B cell responses to subsequent HBV infection that may promote development of CHB in HBV/HIV co-infection. Funding. National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation. 

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