B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin
Emily S. Ford, Anton M. Sholukh, RuthMabel Boytz, Savanna S. Carmack, Alexis Klock, Khamsone Phasouk, Danica Shao, Raabya Rossenkhan, Paul T. Edlefsen, Tao Peng, Christine Johnston, Anna Wald, Jia Zhu, Lawrence Corey
Emily S. Ford, Anton M. Sholukh, RuthMabel Boytz, Savanna S. Carmack, Alexis Klock, Khamsone Phasouk, Danica Shao, Raabya Rossenkhan, Paul T. Edlefsen, Tao Peng, Christine Johnston, Anna Wald, Jia Zhu, Lawrence Corey
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Research Article Immunology Infectious disease

B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin

Abstract

Tissue-based T cells are important effectors in the prevention and control of mucosal viral infections; less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in inflammatory infiltrates in skin biopsy specimens from study participants during symptomatic herpes simplex virus 2 (HSV-2) reactivation and early healing. Both CD20+ B cells, most of which are antigen inexperienced based on their coexpression of IgD, and ASCs — characterized by dense IgG RNA expression in combination with CD138, IRF4, and Blimp-1 RNA — were found to colocalize with T cells. ASCs clustered with CD4+ T cells, suggesting the potential for crosstalk. HSV-2–specific antibodies to virus surface antigens were also present in tissue and increased in concentration during HSV-2 reactivation and healing, unlike in serum, where concentrations remained static over time. B cells, ASCs, and HSV-specific antibody were rarely detected in biopsies of unaffected skin. Evaluation of samples from serial biopsies demonstrated that B cells and ASCs followed a more migratory than resident pattern of infiltration in HSV-affected genital skin, in contrast to T cells. Together, these observations suggest the presence of distinct phenotypes of B cells in HSV-affected tissue; dissecting their role in reactivation may reveal new therapeutic avenues to control these infections.

Authors

Emily S. Ford, Anton M. Sholukh, RuthMabel Boytz, Savanna S. Carmack, Alexis Klock, Khamsone Phasouk, Danica Shao, Raabya Rossenkhan, Paul T. Edlefsen, Tao Peng, Christine Johnston, Anna Wald, Jia Zhu, Lawrence Corey

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Figure 3

IgG RNA+ cells in relation to other tissue structures and cell types.

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IgG RNA+ cells in relation to other tissue structures and cell types. (A...
(A) ASCs are found infiltrating tissue distant from vascular structures, as well as adjacent to and within small capillaries. IgG-producing cells identified by FISH in a healing biopsy are found independently in tissue (lower left) as well as proximate to small capillaries (lower right) in biopsy specimens taken during healing after HSV-2 reactivation. Faint green signal is due to collagen autofluorescence. Blood vessel endothelial cells identified by vWF IF (green); IgG RNA+ cells, magenta. Scale bars: 200 μm; insets, 25 μm. vWF and IgG colocalization by combination FISH and IF was performed in specimens from 6 participants. While capillaries were identified in all samples, IgG cells were not present within these vascular structures in all samples. (B) IgG-producing cells by FISH (left) clustered in an area of dense T cell infiltration (right). CD4, green; CD8, red. Shown are serial sections of the same specimen. Scale bars: 50 μm. IgG FISH and T cell IF were performed in serial biopsy specimens from 4 participants. (C) Clustered IgG (red) and CD4 (green) by FISH; absence of vWF staining was confirmed. Scale bar: 50 μm. IgG and CD4 FISH was performed in specimens from 8 participants.