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

E Derudder, EJ Cadera, JC Vahl, J Wang, CJ Fox… - Nature …, 2009 - nature.com
E Derudder, EJ Cadera, JC Vahl, J Wang, CJ Fox, S Zha, G Van Loo, M Pasparakis
Nature immunology, 2009nature.com
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 …
Abstract
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.
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