Development of immunoglobulin λ-chain-positive B cells, but not editing of immunoglobulin κ-chain, depends on NF-κB signals

By genetically ablating IκB kinase (IKK)-mediated activation of the transcription factor NF-κB in the B cell lineage and by analyzing a mouse mutant in which immunoglobulin λ-chain-positive B cells are generated in the absence of rearrangements in the locus encoding immunoglobulin κ-chain, we define here two distinct, consecutive phases of early B cell development that differ in their dependence on IKK-mediated NF-κB signaling. During the first phase, in which NF-κB signaling is dispensable, predominantly κ-chain-positive B cells are generated, which undergo efficient receptor editing. In the second phase, predominantly λ-chain-positive B cells are generated whose development is ontogenetically timed to occur after rearrangements of the locus encoding κ-chain. This second phase of development is dependent on NF-κB signals, which can be substituted by transgenic expression of the prosurvival factor Bcl-2.