title: Tonic B cell antigen receptor signals supply an NF-kappaB substrate for prosurvival BLyS signaling.
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-kappaB 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.
authors.affiliation: Deparment of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Stadanlick
authors.forename: Mary
authors.initials: M
authors.lastname: Kaileh
authors.forename: Fredrick G
authors.initials: FG
authors.lastname: Karnell
authors.forename: Jean L
authors.initials: JL
authors.lastname: Scholz
authors.forename: Juli P
authors.initials: JP
authors.lastname: Miller
authors.forename: William J
authors.initials: WJ
authors.lastname: Quinn
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Brezski
authors.forename: Laura S
authors.initials: LS
authors.lastname: Treml
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Jordan
authors.forename: John G
authors.initials: JG
authors.lastname: Monroe
authors.forename: Ranjan
authors.initials: R
authors.lastname: Sen
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell