Distinct roles of dendritic cells and macrophages in B cell class switching (39.12)

Abstract

Abstract Immunoglobulin A (IgA) provides the first line of immune protection at mucosal surface. Dendritic cells (DCs) can induce naïve B cell class switching towards IgA in a T cell -independent manner. We questioned whether resident macrophages, antigen presenting cells in tissue, can also shape protective mucosal immunity. Human DCs (by IL-4 and GM-CSF) and macrophages (by M-CSF) were generated from monocytes of the same donor. Autologous IgD+CD27- naïve B cells were activated by anti-IgM (to mimic antigen engagement with BCR), CpG and IL-2, and cultured with DC or macrophages on L cell-coated plates (to mimic stoma environment). We showed here that both anti-inflammatory CD163+ macrophages and DCs induced naïve B cell proliferation and differentiation towards CD38+CD27+CD20- plasmablasts. However, CD38+ cells induced by macrophages showed more terminally differentiated CD138+ plasma cells than those induced by DCs. Macrophage-induced plasma cells preferentially expressed surface IgA whereas DC-induced plasma cells preferentially expressed surface IgG. ELISA showed that macrophage-stimulated B cells produce more IgA (both IgA1 and IgA2) than DC-stimulated B cells which produce more IgG. Macrophage-primed plasma cells also expressed more CCR10 than those primed by DCs. Both tonsil and colon sections confirmed that CD138+ plasma cells were surrounded prevalently by CD163+ resident macrophages. Our data suggest a previously unrecognized mechanism by which macrophages help B cells to establish protective mucosal immunity.