Human IgM Responses to Gut Microbiota

Secretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM+ plasma cells (PCs) were more abundant in humans than mice and clonally related to a large repertoire of memory IgM+ B cells disseminated throughout the intestine but rare in systemic lymphoid organs. Besides sharing a gut-specific signature with memory IgA+ B cells, memory IgM+ B cells interrelated with some IgA+ clonotypes and switched to IgA in response to T cell-independent or T cell-dependent signals. These signals induced abundant IgM, which recognized mucus-embedded commensals as SIgM from clonally affiliated PCs did. Unlike its murine counterpart, human SIgM recognized bacteria dually coated by SIgA that were characterized by increased diversity and richness compared to IgA-only-coated or uncoated bacteria. Thus, SIgM emerges from pre-existing memory rather than newly activated naïve IgM+ B cells and may help SIgA to anchor highly diverse commensal communities to intestinal mucus.