Tonic B cell antigen receptor signals supply an NF-κB substrate for prosurvival BLyS signaling

Jason E. Stadanlick, Mary Kaileh, Fredrick G. Karnell, Jean L. Scholz, Juli P. Miller, William J. Quinn, Randall J. Brezski, Laura S. Treml, Kimberly A. Jordan, John G. Monroe, Ranjan Sen, Michael P. Cancro

Research output: Contribution to journalArticle

Abstract

The survival of transitional and mature B cells requires both the B cell antigen receptor (BCR) and BLyS receptor 3 (BR3), which suggests that these receptors send signals that are nonredundant or that engage in crosstalk with each other. Here we show that BCR signaling induced production of the nonclassical transcription factor NF-κB pathway substrate p100, which is required for transmission of BR3 signals and thus B cell survival. The capacity for sustained p100 production emerged during transitional B cell differentiation, the stage at which BCR signals begin to mediate survival rather than negative selection. Our findings identify a molecular mechanism for the reliance of primary B cells on continuous BR3 and BCR signaling, as well as for the gradual resistance to negative selection that is acquired during B cell maturation.

Original languageEnglish (US)
Pages (from-to)1379-1387
Number of pages9
JournalNature Immunology
Volume9
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Stadanlick, J. E., Kaileh, M., Karnell, F. G., Scholz, J. L., Miller, J. P., Quinn, W. J., Brezski, R. J., Treml, L. S., Jordan, K. A., Monroe, J. G., Sen, R., & Cancro, M. P. (2008). Tonic B cell antigen receptor signals supply an NF-κB substrate for prosurvival BLyS signaling. Nature Immunology, 9(12), 1379-1387. https://doi.org/10.1038/ni.1666