Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals.
By genetically ablating IkappaB kinase (IKK)-mediated activation of the transcription factor NF-kappaB in the B cell lineage and by analyzing a mouse mutant in which immunoglobulin lambda-chain-positive B cells are generated in the absence of rearrangements in the locus encoding immunoglobulin kappa-chain, we define here two distinct, consecutive phases of early B cell development that differ in their dependence on IKK-mediated NF-kappaB signaling. During the first phase, in which NF-kappaB signaling is dispensable, predominantly kappa-chain-positive B cells are generated, which undergo efficient receptor editing. In the second phase, predominantly lambda-chain-positive B cells are generated whose development is ontogenetically timed to occur after rearrangements of the locus encoding kappa-chain. This second phase of development is dependent on NF-kappaB signals, which can be substituted by transgenic expression of the prosurvival factor Bcl-2.
Immune Disease Institute, Boston, Massachusetts, USA. derudder@idi.harvard.edu
Emmanuel
E
Derudder
Emily J
EJ
Cadera
J Christoph
JC
Vahl
Jing
J
Wang
Casey J
CJ
Fox
Shan
S
Zha
Geert
G
van Loo
Manolis
M
Pasparakis
Mark S
MS
Schlissel
Marc
M
Schmidt-Supprian
Klaus
K
Rajewsky
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D051550:I-kappa B Kinase / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D047908:Intracellular Signaling Peptides and Proteins; C514981:NEMO protein, mouse; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D051550:I-kappa B Kinase