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

Nature Immunology volume 10, pages 647–654 (2009)Cite this article

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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Figure 1: B cell development in the absence of NF-κB signaling.
Figure 2: B cell numbers during B cell development in the presence and absence of NF-κB signaling.
Figure 3: Generation of λ-chain-positive B cells in the presence and absence of IKK-mediated NF-κB activation.
Figure 4: Effect of the presence or absence of IKK-mediated activation of NF-κB on receptor editing at the Igk locus.
Figure 5: Effect of overexpression of Bcl-2 in the B cell lineage on the generation of λ-chain-positive B cells in the presence and absence of IKK-mediated NF-κB activation.
Figure 6: Generation of immature NEMO-deficient λ-chain-positive B cells in the presence and absence of rearrangements at Igk loci.

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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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Author notes

  1. Marc Schmidt-Supprian and Klaus Rajewsky: These authors contributed equally to this work.

Authors and Affiliations

  1. Immune Disease Institute, Boston, Massachusetts, USA

    Emmanuel Derudder, J Christoph Vahl, Jing Wang, Marc Schmidt-Supprian & Klaus Rajewsky

  2. Department of Molecular & Cell Biology, University of California at Berkeley, Berkeley, California, USA

    Emily J Cadera & Mark S Schlissel

  3. Max Planck Institute of Biochemistry, Martinsried, Germany

    J Christoph Vahl & Marc Schmidt-Supprian

  4. The Jackson Laboratory, Bar Harbor, Maine, USA

    Casey J Fox

  5. Department of Genetics, Howard Hughes Medical Institute, Children's Hospital, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, USA

    Shan Zha

  6. Department for Molecular Biomedical Research, VIB and Ghent University, Gent-Zwijnaarde, Belgium

    Geert van Loo

  7. Institute for Genetics, Centre for Molecular Medicine, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany

    Manolis Pasparakis

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Correspondence to Emmanuel Derudder, Marc Schmidt-Supprian or Klaus Rajewsky.

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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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