Igλ(+) B cell development but not Igκ editing depends on NF-κB signals

By genetically ablating IκB kinase (IKK)-mediated NF-κB activation in the B cell lineage, and by analyzing a mouse mutant in which Igλ(+) B cells are generated in the absence of rearrangements in Igk, we define 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 Igκ(+) B cells are generated and undergo efficient receptor editing. In the second phase, predominantly Igλ(+) B cells are generated, whose development is ontogenetically timed to occur after Igk rearrangements. This second phase of development is dependent on NF-κB signals, which can be substituted by transgenic expression of the pro-survival factor Bcl2.