Secreted IgM modulates IL-10 expression in B cells.

IL-10 + B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10 + B cell differentiation are ill-defined. Here we find that IL-10 + B cells expand in mice lacking secreted IgM ((s)IgM -/- ) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10 + B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10 + B cells. Lack of the high affinity receptor for sIgM, FcμR, in B cells translates into an intermediate IL-10 + B cell phenotype relative to WT or sIgM -/- mice. Our study thus shows that sIgM regulates IL-10 programming in B cells in part via B cell-expressed FcμR, thereby revealing a function of sIgM in regulating immune homeostasis.