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

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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  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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