Presentation of high antigen‐dose by splenic B220lo B cells fosters a feedback loop between T helper type 2 memory and antibody isotype switching

Effective humoral immunity ensues when antigen presentation by B cells culminates in productive cooperation with T lymphocytes. This collaboration, however, remains ill‐defined because naive antigen‐specific B cells are rare and difficult to track in vivo. Herein, we used a defined transfer model to examine how B lymphocytes, as antigen‐presenting cells, shape the development of T‐cell memory suitable for generation of relevant antibody responses. Specifically, we examined how B cells presenting different doses of antigen during the initial priming phase shape the development of CD4 T‐cell memory and its influence on humoral immunity. The findings indicate that B cells presenting low dose of antigen favour the development of T helper type 1 (Th1) type memory, while those presenting a high antigen dose yielded better Th2 memory cells. The memory Th2 cells supported the production of antibodies by effector B cells and promoted isotype switching to IgG1. Moreover, among the B‐cell subsets tested for induction of Th2 memory, the splenic but not peritoneal B220^lo cells were most effective in sustaining Th2 memory development as well as immunoglobulin isotype switching, and this function involved a tight control by programmed death 1–programmed death ligand 2 interactions.