Intestine-specific CCR10+ plasma cells regulate migration of intestinal regulatory T cells

Abstract

Abstract In intestines, B cells are activated in gut-associated lymphoid tissue (GALT) to differentiate predominantly to IgA antibody-secreting cells (IgA-ASCs), which acquire a CCR10+ specific gut-homing property and migrate into intestinal lamina propria where they secrete IgA antibodies specifically acting on commensal bacteria and food-borne antigens for homeostatic regulation. While IgA antibodies were extensively investigated, differentiation of B cells and their functional mechanisms in establishment of intestinal homeostasis are still incompletely understood. We herein report a novel process in which CCR10+ differentiated B cells regulate intestinal homeostasis. We found that CCR10+ IgA-ASCs preferentially interact with activated regulatory T (Treg) cells in GALT and lamina propria to help their localization in colons. In CCR10-knockout mice, defective intestinal migration of IgA-ASCs resulted in reduced Treg cells and spontaneous development of inflammatory symptoms in colons. In addition, in IgA-deficient mice, there was preferential compensatory generation of CCR10+ IgG-ASCs that substituted CCR10+ IgA-ASCs to promote T cell homeostasis and regulate commensal bacteria in colons. The preferential compensatory generation of CCR10+ IgG-ASCs was also observed in IgA-deficient patients. These findings aid our understanding of B cell differentiation and functional mechanisms in intestinal homeostatic regulation.