Natural IgM Is Required for Suppression of Inflammatory Arthritis by Apoptotic Cells

Abstract

The clearance of dying cells is vital for re-establishing tolerance during inflammation and has potent immunoregulatory consequences. Because natural IgM plays a key role in the removal of apoptotic cells, we investigated whether the immune modulatory properties of apoptotic cells depended on its presence. Using an Ab-independent, Ag-induced model of inflammatory arthritis, we tested whether natural IgM is essential for the arthritis-suppressing properties of apoptotic cells. Whereas administration of apoptotic cells reduced joint inflammation and damage in normal mice accompanied by suppression of the Th17 response, no protection was afforded in secreted IgM-deficient (Sμ–) mice. The enhanced production of IL-10 by T cells from draining lymph nodes and splenic marginal zone B cells, driven by the infusion of apoptotic cells, was abrogated in the absence of natural IgM. Apoptotic cells were present shortly after administration in the splenic marginal zone, but their removal was substantially delayed in the absence of natural IgM. Incubation of apoptotic cells with natural IgM in vitro restored their arthritis-suppressing properties in Sμ– mice. Moreover, these IgM-coated apoptotic cells were cleared rapidly after injection from the spleens of Sμ– mice. Our results demonstrate that natural IgM is a critical factor in a chain of events triggered by the administration of apoptotic cells that promote IL-10–secreting B and T cells and restrain the development of inflammation.

Eicosapentaenoic and docosahexaenoic acid ethyl esters differentially enhance B-cell activity in murine obesity

“…The lack of improvement The results open the door to the possibility that DHA may increase IL-10 secretion from B cells in vivo, which could be driven by natural IgM. Natural IgM increases phagocytosis of apoptotic cells in the marginal zone to increase IL-10-secreting B cells ( 24,36 ). Furthermore, improving IL-10 secretion in the adipose is of particular signifi cance because IL-10-secreting B cells improve insulin sensitivity in obesity ( 37 ).…”

A tolerogenic role for Toll-like receptor 9 is revealed by B-cell interaction with DNA complexes expressed on apoptotic cells

“…ACs also protect mice from autoimmune-mediated inflammation (6,7) and induce B cells to adopt an IL-10-secreting regulatory B-cell phenotype (Breg) (8). Innate-like B cells have many selfreactive B-cell receptors (BCRs) and are selected by intracellular antigens expressed on ACs (9), but this is generally compatible with health (10)(11)(12)(13).…”

Anti‐TIM‐1 Monoclonal Antibody (RMT1‐10) Attenuates Atherosclerosis By Expanding IgM‐producing B1a Cells

“…Lipid and macrophage accumulation were also markedly reduced, by 40% and 38%, respectively, (all P <0.05; Figures 5A and 5B), however the ratio of lipid and macrophage accumulation was not affected (Figure 4B). Because IgM facilitates removal of apoptotic cells,33, 34 we assessed the effects of RMT1‐10 treatment on lesion apoptotic cell numbers. Treatment with RMT1‐10 reduced apoptotic cell numbers in lesions by 30% ( P <0.05; Figure 5C).…”