B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota

eLife

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[1] Center for Comparative Medicine, University of California, Davis, Davis, United States;Department of Genetics, Stanford University, Stanford, United States;Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;

关键词: B cells;    microbiota;    Toll-like receptors;    antibodies;    Mouse;   

DOI  :  10.7554/eLife.47015

来源: publisher

【 摘 要 】

10.7554/eLife.47015.001B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of ‘natural’ IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood. Here, we use a novel reporter mouse to demonstrate that production of self- and microbiota-reactive antibodies is linked to BCR signaling in B-1a cells. Moreover, we show that Toll-like receptors (TLRs) are critical for shaping the Ig repertoire of B-1a cells as well as regulating their antibody production. Strikingly, we find that both the colonization of a microbiota as well as microbial-sensing TLRs are required for anti-microbiota B-1a responses, whereas nucleic-acid sensing TLRs are required for anti-PtC responses, demonstrating that linked activation of BCR and TLRs controls steady state B-1a responses to both self and microbiota-derived antigens.

【 授权许可】

CC BY