Article abstract
Nature Immunology 9, 1379 - 1387 (2008)
Published online: 2 November 2008 | doi:10.1038/ni.1666
Tonic B cell antigen receptor signals supply an NF-
B substrate for prosurvival BLyS signaling
Jason E Stadanlick1, Mary Kaileh2, Fredrick G Karnell1, Jean L Scholz1, Juli P Miller1, William J Quinn III1, Randall J Brezski1, Laura S Treml1, Kimberly A Jordan3, John G Monroe1, Ranjan Sen2 & Michael P Cancro1
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-
B 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.
- Deparment of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
- Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
- Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA.
Correspondence to: Michael P Cancro1 e-mail: cancro@mail.med.upenn.edu
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