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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Acknowledgements
We regret that for space reasons we often had to quote reviews instead of the original papers. We thank S. Akira (Osaka University), F. Alt (Children's Hospital, Boston), R. Bram (Mayo Medical School, Rochester), R. Geha (Children's Hospital, Boston), T. Mak (Campbell Family Institute for Cancer Research), D. Nemazee (The Scripps Research Institute) and M. Reth (University of Freiburg) for Myd88−/−, Atm−/−, Taci−/−, Bcl10−/−, κ-macroself and mb1-cre cells and mouse strains; S. Weiss (Helmholtz Centre for Infection Research) for anti-λ1-chain; N. Rice (US National Cancer Institute) for anti-p52; T. Chakraborty, G. Galler and S. Koralov for help with quantitative real-time PCR, EMSA and cell-cycle analysis; M. Bamberg for antibody preparation; N. Barteneva for cell sorting; and D. Ghitza, A. Pellerin, J. Grundy and J. Xia for technical assistance with mouse work. Supported by the US National Institutes of Health (M.S.S. and K.R.) and Deutsche Forschungsgemeinschaft (Emmy Noether grant to M.S.-S.).
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Derudder, E., Cadera, E., Vahl, J. et al. Development of immunoglobulin λ-chain–positive B cells, but not editing of immunoglobulin κ-chain, depends on NF-κB signals. Nat Immunol 10, 647–654 (2009). https://doi.org/10.1038/ni.1732
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DOI: https://doi.org/10.1038/ni.1732
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