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IgD can largely substitute for loss of IgM function in B cells

Nature volume 393, pages 797–801 (1998)Cite this article

Abstract

The μ and δ heavy chains of IgM and IgD, the first antibody isotypes expressed during bone-marrow B-cell development, are encoded by a common transcription unit. Expression of the μ chain on the surface of late pre-B cells allows their further development to immature B cells. Coexpression of the δ chain and emigration of the immature B cells to the periphery eventually leads to the development of naive mature IgM/IgD double-positive cells. Although IgM is important in driving B-cell development1, the contribution of IgD is not clear. Here we investigate the function of IgD. We generated mice deficient in IgM (IgM−/− mice) by deleting the μ region in embryonic stem cells. IgM−/− mice showed normal B-cell development and maturation, with IgD replacing membrane-bound and secretory IgM. Moreover, specific B-cell responses and isotype class switches occurred during immunization or infection. In contrast to mice deficient in B cells, IgM−/− mice survived infection with vesicular stomatitis virus by developing neutralizing immunoglobulins, but they were more susceptible than wild-type controls with delayed specific immunoglobulin responses. These data lead us to conclude that IgD is largely able to substitute for IgM functions.

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Figure 1: Generation of IgM-deficient mice.
Figure 2: Flow cytometric analysis of IgM-deficient (−/−) or wild-type (+/+) mice.
Figure 3: Immunization with antigen.
Figure 4: Germinal centre formation.
Figure 5: Immune responses to VSV in wild-type and IgM−/− mice.

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Acknowledgements

We thank M. Held, C. Westphal, I. Fidler, S. Meier, S. Herren and K.-H. Widmann for technical help, and L. Nitschke, P. Nielsen and M. Reth for discussion and critically reviewing the manuscript.

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Authors and Affiliations

  1. Max-Planck-Institute for Immunobiology, Freiburg, Germany

    Claudia Lutz, Georges Köhler & Frank Brombacher

  2. Novartis Pharma Inc., Research, Basel, Switzerland

    Birgit Ledermann

  3. Geneva Biomedical Research Institute, Glaxo Welcome Research and Development, Plan-les-Quates, Switzerland

    Marie H. Kosco-Vilbois

  4. Institute for Experimental Immunology, Zurich, Switzerland

    Adrian F. Ochsenbein & Rolf M. Zinkernagel

  5. Department of Immunology, University of Cape Town, Groote Schuur Hospital, H47, Observatory, 7925, Cape Town, South Africa

    Georges Köhler

Author notes

  1. This work is dedicated to the memory of Georges Khler who initiated this project.

    • Frank Brombacher
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Correspondence to Frank Brombacher.

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Lutz, C., Ledermann, B., Kosco-Vilbois, M. et al. IgD can largely substitute for loss of IgM function in B cells. Nature 393, 797–801 (1998). https://doi.org/10.1038/31716

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