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

Abstract

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. 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. 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. 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. National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation. .