The skin: a site of extralymphoid IgM production

Abstract

Abstract Antibodies are critical to cutaneous host defense and inflammation, but the mechanisms by which skin antibodies are maintained are poorly described. In this study, we found extralymphoid antibody production in unperturbed human and mouse skin. IgM was the predominant isotype produced by plasma cells in healthy murine skin and was also secreted in healthy human skin. In mice, cutaneous IgM plasma cells were independent of T cells and microbiota. Importantly, chronic inflammation caused the massive accumulation of IgM secreting cells that was dependent on APRIL or BAFF in skin but not in other sites. In addition, skin immunization caused cutaneous accumulation of both T cell-dependent and -independent antigen-specific IgM secreting cells. Thus, we reveal the skin as a novel niche for plasma cells with important implications for the regulation of cutaneous antibodies. We propose that skin plasma cells supply natural and adaptive IgM to the cutaneous environment, thereby supporting homeostatic skin barrier functions in addition to providing defense against pathogen intrusion.