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
View: Text | PDF
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

×

Figure 3

Unsupervised FlowSOM clustering reveals a Breg population upregulated in MWH who develop CHB.

Options: View larger image (or click on image) Download as PowerPoint
Unsupervised FlowSOM clustering reveals a Breg population upregulated in...
(A) Comparison of FlowSOM cluster abundance by HBV outcome in MWoH and MWH by Wilcoxon’s signed-rank test is shown. Volcano plot depicts –log10-transformed unadjusted P values and log2 fold-change of cluster abundance in controllers compared with CHB. Upper right quadrant depicts clusters significantly upregulated in controllers while upper left quadrant depicts clusters significantly upregulated in CHB. Each dot represents a FlowSOM cluster colored by time point (red, preinfection; orange, acute; light green, early outcome; dark green, late outcome). (B) FlowSOM cluster 31 abundance in MWoH and MWH stratified by HBV outcome is shown. Each dot represents 1 sample for each participant at given time point (see Figure 2 legend for sample numbers). Box plots show median, quartile, and minimum/maximum. Data compared using Wilcoxon’s signed-rank test. P values are unadjusted for multiple comparisons. (C and D) Histogram plots show expression of all lineage markers (C) and phenotypic markers (D) for total B cells (gray) compared with FlowSOM cluster 31 (blue). (E) FlowSOM cluster 31 abundance compared between MWH controllers, MWH CHB with high CD4+ counts (>350 cells/mL), and MWH CHB with low CD4+ counts (<350 cells/mL) using a GEE regression model. Each dot represents 1 sample, colored by time point. P values were obtained from the GEE model. *, P < 0.05; **, P < 0.01; ****, P < 0.0001.