Human IgM^hiCD300a⁺ B Cells Are Circulating Marginal Zone Memory B Cells That Respond to Pneumococcal Polysaccharides and Their Frequency Is Decreased in People Living with HIV

CD300a is differentially expressed among B cell subsets, although its expression in immunoglobulin (Ig)M⁺ B cells is not well known. We identified a B cell subset expressing CD300a and high levels of IgM (IgM^hiCD300a⁺). The results showed that IgM^hiCD300a⁺ B cells were CD10^-CD27⁺CD25⁺IgD^loCD21^hiCD23^-CD38^loCD1c^hi, suggesting that they are circulating marginal zone (MZ) IgM memory B cells. Regarding the immunoglobulin repertoire, IgM^hiCD300a⁺ B cells exhibited a higher mutation rate and usage of the IgH-VDJ genes than the IgM⁺CD300a^- counterpart. Moreover, the shorter complementarity-determining region 3 (CDR3) amino acid (AA) length from IgM^hiCD300a⁺ 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 toll-like receptor 9 (TLR9) agonist than IgM⁺CD300a^- cells. Finally, the frequency of IgM^hiCD300a⁺ B cells was lower in people living with HIV-1 (PLWH) and it was inversely correlated with 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.