Tonic B cell antigen receptor signals supply an NF-kappaB substrate for prosurvival BLyS signaling.
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.
Stadanlick
Jason E
JE
Deparment of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Kaileh
Mary
M
Karnell
Fredrick G
FG
Scholz
Jean L
JL
Miller
Juli P
JP
Quinn
William J
WJ
Brezski
Randall J
RJ
Treml
Laura S
LS
Jordan
Kimberly A
KA
Monroe
John G
JG
Sen
Ranjan
R
Cancro
Michael P
MP
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*
D053264:B-Cell Activating Factor; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell