Secreted IgM modulates IL-10 expression in B cells
Shannon E. McGettigan, Lazaro E. Aira, Gaurav Kumar, Romain Ballet, Eugene C. Butcher, Nicole Baumgarth, Gudrun F. Debes
Abstract
Abstract 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.