HIV causes global B-cell dysregulation and restricts HBV-specific B-cell development in an incident HBV cohort
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 co-infection. METHODS: 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. 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 (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. CONCLUSION: 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. FUNDING: National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation. .
Authors
- Katherine Cascino (ORCID: https://orcid.org/0000-0001-7308-5162)
- Robbie B. Mailliard (ORCID: https://orcid.org/0000-0001-5501-503X)
- Chloe L. Thio (ORCID: https://orcid.org/0000-0002-8851-8319)
- Kathleen Stevens (ORCID: https://orcid.org/0000-0003-1410-5471)
- Thomas Liechti (ORCID: https://orcid.org/0000-0001-8738-6679)
- Andrea L. Cox (ORCID: https://orcid.org/0000-0002-9331-2462)
- Justin Bailey
- Mallory D. Witt
- Steven M. Wolinsky
- Mario Roederer
Institutions
- Northwestern University (US)
- National Institutes of Health (US)
- Johns Hopkins University (US)
- University of Pittsburgh (US)
- Johns Hopkins Medicine (US)
- UCLA Medical Center (US)
- Harbor–UCLA Medical Center (US)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2026-04-07
- DOI
- https://doi.org/10.1172/jci203138
- Primary Topic
- Hepatitis B Virus Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- Gilead Sciences
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- University of California, San Francisco
- Center for AIDS Research, University of Alabama at Birmingham
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Aging
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Cancer Institute
- National Institute on Deafness and Other Communication Disorders
- National Institute of Nursing Research
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute of Dental and Craniofacial Research
- National Institute on Minority Health and Health Disparities
- Center for AIDS Research, University of North Carolina at Chapel Hill
- Clinical and Translational Science Institute, University of California, Los Angeles