Regulation of dendritic cells and macrophages by an anti-apoptotic-cell natural antibody that suppresses TLR responses and inhibits inflammatory arthritis

摘要: Although natural Abs (NAbs) are present from birth, little is known about what drives their selection and whether they have housekeeping functions. The prototypic T15-NAb, first identified because of its protective role in infection, representative a special type NAb response that specifically recognizes forms complexes with apoptotic cells which promotes cell-corpse engulfment by phagocytes. We now show this T15-NAb IgM-mediated clearance process dependent on the recruitment C1q mannose-binding lectin, immune modulatory activities also provide "eat me" signals for enhancing phagocytosis. Further investigation revealed addition significantly suppressed vitro LPS-induced TNF-alpha IL-6 secretion macrophage-like cell line, RAW264.7, as well TLR3-, TLR4-, TLR7-, TLR9-induced maturation range proinflammatory cytokines chemokines bone marrow-derived conventional dendritic cells. Significantly, high doses B-1 produced vivo TLR-induced responses. infusions such inflammatory responses effect was associated induction levels IgM antiapoptotic Abs, treatment not effective at suppressing TLR B cell-deficient mice. Moreover, efficiently inhibited both collagen-induced arthritis anti-collagen II Ab-mediated arthritis. These studies identify characterize previously unknown regulatory circuit product innate-like aids homeostasis control fundamental pathways.