Title

Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals.

Document Type

Article

Publication Date

2009

Keywords

B-Lymphocytes, Cell-Differentiation, I-kappa-B-Kinase, Immunoglobulin-kappa-Chains, Immunoglobulin-lambda-Chains, Intracellular-Signaling-Peptides-and-Proteins, Mice-Inbred-C57BL, Mice-Knockout, Mice-Transgenic, NF-kappa-B, Proto-Oncogene-Proteins, Signal-Transduction

JAX Source

Nat Immunol 2009 Jun; 10(6):647-54.

Abstract

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.