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Secondary V(D)J recombination in B-1 cells

Nature volume 397, pages 355–359 (1999)Cite this article

Abstract

B-1 B cells are a self-renewing population of B cells that differ from conventional B cells (B-2 cells) in that they are particularly predisposed to auto-antibody production1,2,3. Although much is known about the signalling pathways that control B-1-cell growth and development (reviewed in ref. 4), less is known about why these cells are prone to produce autoreactive antibodies. Here we show that B-1 cells, like germinal-centre B cells5,6,7,8, can express recombinase-activating genes 1 and 2 (RAG1 and RAG2) and undergo secondary V(D)J recombination of immunoglobulin genes. In addition, B cells from autoimmune-prone NZB mice show high levels of RAG messenger RNA and recombination. We propose that secondary immunoglobulin-gene rearrangements outside organized lymphoid organs may contribute to the development of autoreactive antibodies.

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Figure 1: Loss of expression of the Ac146 idiotype on peritoneal B cells.
Figure 2: Loss of idiotype expression is dependent on V(D)J recombination.
Figure 3: Secondary V(D)J-recombination activity in peritoneal B cells.
Figure 4: Absence of B-1 cells in B1-8Hi+/−3-83κi+/−Ku80−/− mice.
Figure 5: Increased expression of RAG1 and RAG2 and secondary V(D)J-recombination activity in peritonea.

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Acknowledgements

We thank members of the Nussenzweig lab for comments on the manuscript and helpful discussions. This work was supported by grants from the NIH (to M.C.N.) and the Deutsche Forschungsgemeinschaft (through SFB243) and the EU (to K.R.). X-F.Q. was supported by an RU graduate fellowship and NIH training grant. A.N. was supported in part by a grant from the Arthritis Foundation. M.C.N. is an associate investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Laboratory of Molecular Immunology, The Rockefeller University, New York, 10021, New York, USA

    Xiao-Feng Qin, Wong Yu, Fotini Papavasiliou, Heikyung Suh & Michel C. Nussenzweig

  2. Howard Hughes Medical Institute The Rockefeller University, New York, 10021, New York, USA

    Heikyung Suh & Michel C. Nussenzweig

  3. Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Andre Nussenzweig

  4. Institute for Genetics, University of Cologne, 50931, Weyertal, Germany

    Stephan Schwers & Klaus Rajewsky

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Correspondence to Michel C. Nussenzweig.

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Qin, XF., Schwers, S., Yu, W. et al. Secondary V(D)J recombination in B-1 cells. Nature 397, 355–359 (1999). https://doi.org/10.1038/16933

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