HIV causes global B cell dysregulation and restricts HBV-specific B cell development in an incident HBV cohort
Katherine Cascino, Thomas Liechti, Eric C. Seaberg, Kathleen E. Stevens, Steven M. Wolinsky, Mallory D. Witt, Robbie B. Mailliard, Mario Roederer, Justin R. Bailey, Chloe L. Thio, Andrea L. Cox
Katherine Cascino, Thomas Liechti, Eric C. Seaberg, Kathleen E. Stevens, Steven M. Wolinsky, Mallory D. Witt, Robbie B. Mailliard, Mario Roederer, Justin R. Bailey, Chloe L. Thio, Andrea L. Cox
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Clinical Research and Public Health Immunology Virology

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

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 coinfection.METHODS Here, we employed high-dimensional single-cell analysis to assess global and hepatitis B surface antigen–specific (HBsAg-specific) B cells in a longitudinal cohort of incident HBV from the Multicenter AIDS Cohort Study, 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 B cells and regulatory B cells, 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 monoinfection, 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 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 coinfection.FUNDING Vaccine Research Center, NIAID, Bill & Melinda Gates Foundation, and NIH.

Authors

Katherine Cascino, Thomas Liechti, Eric C. Seaberg, Kathleen E. Stevens, Steven M. Wolinsky, Mallory D. Witt, Robbie B. Mailliard, Mario Roederer, Justin R. Bailey, Chloe L. Thio, Andrea L. Cox

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Figure 5

Expanded HBsAg-specific B cells are phenotypically heterogeneous.

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Expanded HBsAg-specific B cells are phenotypically heterogeneous. (A) Vo...
(A) Volcano plots depict log2 fold-change and –log10-transformed unadjusted P values based on comparisons of HBsAg-specific B cell abundance by FlowSOM cluster between each possible combination of time points in HBV controllers. P values calculated by Wilcoxon’s signed-rank test. Each dot represents a FlowSOM cluster, colored by HIV-1 infection status (MWoH, yellow; MWH, purple). (B) The log10-transformed frequency of HBsAg-specific B cells over time is plotted for both MWoH and MWH controllers in 10 clusters of interest. Top row consists of clusters upregulated in MWoH; bottom row are clusters upregulated in MWH. Abundances lower than 0.01% were adjusted to 0.01% for visualization but not statistical analysis purposes. Each dot represents 1 sample at a given time point. Data compared by Wilcoxon’s signed-rank test with Bonferroni’s correction for multiple testing. *, P < 0.05; **, P < 0.01; ***, P < 0.001. (C) Previously generated UMAP of total B cells overlaid with HBsAg-specific B cells from 10 clusters of interest are colored by FlowSOM cluster. HBsAg-specific B cells are plotted on zoomed-in sections of total UMAP (top row: expanded in MWoH; bottom row: expanded in MWH). (C and D) Histogram plots show expression levels for all lineage markers (C) and phenotypic markers (D) assessed in the panel for each of the 10 FlowSOM clusters compared with total B cells (gray histograms).