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