NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome

Kyoko Hayakawa, Anthony M. Formica, Yan Zhou, Daiju Ichikawa, Masanao Asano, Yue Sheng Li, Susan A. Shinton, Joni Brill-Dashoff, Gabriel Núñez, Richard R. Hardy

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2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3067-3083
Number of pages17
JournalJournal of Experimental Medicine
Volume214
Issue number10
DOIs
Publication statusPublished - 2017 Jan 1

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hayakawa, K., Formica, A. M., Zhou, Y., Ichikawa, D., Asano, M., Li, Y. S., Shinton, S. A., Brill-Dashoff, J., Núñez, G., & Hardy, R. R. (2017). NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome. Journal of Experimental Medicine, 214(10), 3067-3083. https://doi.org/10.1084/jem.20170497