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Hayakawa K , Formica AM , Zhou Y , Ichikawa D , Asano M , Li YS , Shinton SA , Brill-Dashoff J , Nunez G , Hardy RR
NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome
J Exp Med. 2017 Oct 02;214(10) :3067-3083
PMID: 28878001 PMCID: PMC5626402
AbstractAlthough B cell development requires expression of the B cell antigen receptor (BCR), it remains unclear whether engagement of self-antigen provides a positive impact for most B cells. Here, we show that BCR engagement by self-ligand during development in vivo results in up-regulation of the Nod-like receptor member Nod1, which recognizes the products of intestinal commensal bacteria. In anti-thymocyte/Thy-1 autoreactive BCR knock-in mice lacking self-Thy-1 ligand, immunoglobulin light chain editing occurred, generating B cells with up-regulated Nod1, including follicular and marginal zone B cells with natural autoreactivity. This BCR editing with increased Nod1 resulted in preferential survival. In normal adult mice, most mature B cells are enriched for Nod1 up-regulated cells, and signaling through Nod1 promotes competitive survival of mature B cells. These findings demonstrate a role for microbial products in promoting survival of mature B cells through up-regulated Nod1, providing a positive effect of BCR engagement on development of most B cells.
Notes1540-9538 Hayakawa, Kyoko ORCID: http://orcid.org/0000-0003-3157-5897 Formica, Anthony M ORCID: http://orcid.org/0000-0002-9209-0335 Zhou, Yan ORCID: http://orcid.org/0000-0002-8698-0040 Ichikawa, Daiju ORCID: http://orcid.org/0000-0002-5940-2720 Asano, Masanao Li, Yue-Sheng Shinton, Susan A ORCID: http://orcid.org/0000-0003-2649-1904 Brill-Dashoff, Joni ORCID: http://orcid.org/0000-0002-8596-5877 Nunez, Gabriel Hardy, Richard R ORCID: http://orcid.org/0000-0002-9809-5583 R01 DK061707/DK/NIDDK NIH HHS/United States R01 AI026782/AI/NIAID NIH HHS/United States R01 AI113320/AI/NIAID NIH HHS/United States R01 AI049335/AI/NIAID NIH HHS/United States R56 AI026782/AI/NIAID NIH HHS/United States Journal Article United States J Exp Med. 2017 Oct 2;214(10):3067-3083. doi: 10.1084/jem.20170497. Epub 2017 Sep 6.