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J Exp Med ; 214(10): 3067-3083, 2017 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-28878001

RESUMEN

Although 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.


Asunto(s)
Linfocitos B/fisiología , Proteínas NLR/fisiología , Proteína Adaptadora de Señalización NOD1/fisiología , Receptores de Antígenos de Linfocitos B/fisiología , Envejecimiento/fisiología , Animales , Linfocitos B/metabolismo , Técnicas de Sustitución del Gen , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Transducción de Señal/fisiología , Regulación hacia Arriba
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