Figure 1.

B cells differentiate into IgA ASC in the GALT due to the constant stimulation of the immune system by commensal bacteria, invading pathogens as well as food antigens. From there, gut-derived IgA ASC potentially travel through the blood to the PC niches in the BM. There, survival and function of PC can be supported by the secretion of exemplarily indicated survival factors. IgA ASC in the BM are thought to release monomeric IgA antibodies into the bloodstream directed against a variety of pathogens to counter sepsis in case of a microbial breach in the gut. Furthermore, IgA antibodies can be the cause for pathogenic immunoglobulin deposits in kidney glomeruli during autoinflammatory diseases. It is currently unknown, whether or not the infiltration of IgA ASC into the inflamed kidney further boosts disease through local antibody production. Finally, in the CNS, IgA PC protect the blood-brain barrier at the meninges from invading pathogens. Furthermore, gut-derived IgA PC can enter the CNS in inflammatory conditions like MS lesions, where they attenuate neuroinflammation in an IL-10 dependent manner. The brain might also provide factors needed for PC survival and hence constitute a novel PC niche. As more and more evidence points at the possibility of a systemic migration of gut-derived IgA ASC, further survival niches for those cells need to be considered. ASC, antibody secreting cell; GALT, gut associated lymphoid tissue; CNS, central nervous system; BM, bone marrow; PC, plasma cell; SLE, systemic lupus erythematosus; IgAN, IgA nephropathy; IL-10, interleukin-10.