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, Daijyu Ichikawa, Masanao Asano, Yue Sheng Li, Susan A. Shinton, Joni Brill-Dashoff, Gabriel Núñez, Richard R. Hardy

Research output: Contribution to journalArticle

1 Citation (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

Fingerprint

B-Cell Antigen Receptors
B-Lymphocytes
Ligands
Immunoglobulin Light Chains
Autoantigens
Thymocytes
Up-Regulation
Bacteria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome. / Hayakawa, Kyoko; Formica, Anthony M.; Zhou, Yan; Ichikawa, Daijyu; Asano, Masanao; Li, Yue Sheng; Shinton, Susan A.; Brill-Dashoff, Joni; Núñez, Gabriel; Hardy, Richard R.

In: Journal of Experimental Medicine, Vol. 214, No. 10, 2017, p. 3067-3083.

Research output: Contribution to journalArticle

Hayakawa, K, Formica, AM, Zhou, Y, Ichikawa, D, Asano, M, Li, YS, Shinton, SA, Brill-Dashoff, J, Núñez, G & Hardy, RR 2017, 'NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome', Journal of Experimental Medicine, vol. 214, no. 10, pp. 3067-3083. https://doi.org/10.1084/jem.20170497
Hayakawa, Kyoko ; Formica, Anthony M. ; Zhou, Yan ; Ichikawa, Daijyu ; Asano, Masanao ; Li, Yue Sheng ; Shinton, Susan A. ; Brill-Dashoff, Joni ; Núñez, Gabriel ; Hardy, Richard R. / NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome. In: Journal of Experimental Medicine. 2017 ; Vol. 214, No. 10. pp. 3067-3083.
@article{b57c8e0cca7441a991eb1a955631788e,
title = "NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome",
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.",
author = "Kyoko Hayakawa and Formica, {Anthony M.} and Yan Zhou and Daijyu Ichikawa and Masanao Asano and Li, {Yue Sheng} and Shinton, {Susan A.} and Joni Brill-Dashoff and Gabriel N{\'u}{\~n}ez and Hardy, {Richard R.}",
year = "2017",
doi = "10.1084/jem.20170497",
language = "English",
volume = "214",
pages = "3067--3083",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "10",

}

TY - JOUR

T1 - NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome

AU - Hayakawa, Kyoko

AU - Formica, Anthony M.

AU - Zhou, Yan

AU - Ichikawa, Daijyu

AU - Asano, Masanao

AU - Li, Yue Sheng

AU - Shinton, Susan A.

AU - Brill-Dashoff, Joni

AU - Núñez, Gabriel

AU - Hardy, Richard R.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85030648081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030648081&partnerID=8YFLogxK

U2 - 10.1084/jem.20170497

DO - 10.1084/jem.20170497

M3 - Article

VL - 214

SP - 3067

EP - 3083

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 10

ER -