IgM Memory B Cell Heterogeneity in Immune Responses to Pneumococcal Vaccination in HIV-positive and Healthy Individuals

Abstract

Abstract Background: Both normal aging and HIV infection impact B cell functionality and lead to activation of resting B cells, memory cell depletion and altered gene expression. As a result, HIV+ individuals and the elderly fail to demonstrate robust and durable immune responses against pneumococcal polysaccharides. Herein, we assessed altered B cell function in high risk groups by utilizing single cell technology. Methods: HIV-positive individuals with CD4+T cell counts >200 on Antiretroviral Therapy (ART) and HIV-negative individuals age groups 21-40 and 50-65 received pneumococcal vaccination. Serum IgG and IgM PPS-specific antibodies were measured pre- and post-immunization using ELISA method. Evaluation of B cells was performed using flow cytometry and single cell RT-PCR. Results: IgM memory B cells are important players in responding to pneumococcal antigens and are present in reduced quantities in HIV+ and aging HIV- individuals. Single cell analysis of IgM memory B cells demonstrated heterogeneity and identified two unique subpopulations. One of the subpopulations represents B cells with higher expression of TACI and BAFF-R and is more likely to dominate in T-cell independent immune responses. IgD+IgM+memory B cells were present in equal proportions in both subpopulations. Conclusion: Pneumococcal vaccine responses in HIV+ and aging HIV- individuals are multifactorial and largely depend on the abundance and phenotypic characteristics of IgM memory B cells.