
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.
Cell-Differentiation, Immunoglobulin-lambda-Chains, 570, Signal-Transduction, Intracellular-Signaling-Peptides-and-Proteins, 610, Mice, Transgenic, I-kappa-B-Kinase, Mice-Transgenic, Immunoglobulin kappa-Chains, Mice, Immunoglobulin lambda-Chains, Immunoglobulin-kappa-Chains, Proto-Oncogene Proteins, Animals, Proto-Oncogene-Proteins, Mice, Knockout, B-Lymphocytes, Mice-Inbred-C57BL, Intracellular Signaling Peptides and Proteins, NF-kappa B, Cell Differentiation, Mice-Knockout, I-kappa B Kinase, Mice, Inbred C57BL, NF-kappa-B, Proto-Oncogene Proteins c-bcl-2, Signal Transduction
Cell-Differentiation, Immunoglobulin-lambda-Chains, 570, Signal-Transduction, Intracellular-Signaling-Peptides-and-Proteins, 610, Mice, Transgenic, I-kappa-B-Kinase, Mice-Transgenic, Immunoglobulin kappa-Chains, Mice, Immunoglobulin lambda-Chains, Immunoglobulin-kappa-Chains, Proto-Oncogene Proteins, Animals, Proto-Oncogene-Proteins, Mice, Knockout, B-Lymphocytes, Mice-Inbred-C57BL, Intracellular Signaling Peptides and Proteins, NF-kappa B, Cell Differentiation, Mice-Knockout, I-kappa B Kinase, Mice, Inbred C57BL, NF-kappa-B, Proto-Oncogene Proteins c-bcl-2, Signal Transduction
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