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

First Author  Kreuk LS Year  2019
Journal  Elife Volume  8
PubMed ID  31433298 Mgi Jnum  J:278686
Mgi Id  MGI:6357777 Doi  10.7554/eLife.47015
Citation  Kreuk LS, et al. (2019) B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota. Elife 8:e47015
abstractText  B-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.
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