Human IgMhiCD300a+ B cells are circulating marginal zone memory B cells that respond to pneumococcal polysaccharides and their frequency is decreased in people living with HIV

Abstract

CD300a is differentially expressed among B cell subsets, although its expression on IgM+ B cells is not well known. We have identified a B cell subset expressing CD300a and high levels of IgM (IgMhiCD300a+). Results showed that IgMhiCD300a+ B cells were CD10-CD27+CD25+IgDloCD21hiCD23-CD38loCD1chi, suggesting that they are circulating marginal zone IgM memory B cells. Regarding the immunoglobulin repertoire, IgMhiCD300a+ B cells exhibited a higher mutation rate and usage of the IgH-VDJ genes than the IgM+CD300a- counterpart. Moreover, the shorter CDR3 AA length from IgMhiCD300a+ B cells together with the predicted antigen experience repertoire, indicates that this B cell subset has a memory phenotype. IgM memory B cells are important in T cell-independent responses. Accordingly, we demonstrate that this particular subset secretes higher amounts of IgM after stimulation with pneumococcal polysaccharides or a TLR9 agonist than IgM+CD300a- cells. Finally, the frequency of IgMhiCD300a+ B cells was lower in people living with HIV-1 (PLWH) and it was inversely correlated to the years with HIV infection. Altogether, these data help to identify a memory B cell subset that contributes to T cell-independent responses to pneumococcal infections and may explain the increase in severe pneumococcal infections and the impaired responses to pneumococcal vaccination in PLWH.