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

Nature. 1998 Jun 25;393(6687):797-801. doi: 10.1038/31716.


The mu and delta 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 mu chain on the surface of late pre-B cells allows their further development to immature B cells. Coexpression of the delta 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 development, 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 mu 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.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology*
  • Bone Marrow Cells / cytology
  • Cell Differentiation / immunology
  • Cell Differentiation / physiology
  • Immunoglobulin D / physiology*
  • Immunoglobulin M / deficiency
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Immunoglobulin M / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mutagenesis
  • Peritoneal Cavity / cytology
  • Receptors, Antigen, B-Cell / immunology
  • Spleen / cytology
  • Stem Cells
  • Vesicular stomatitis Indiana virus / immunology


  • Immunoglobulin D
  • Immunoglobulin M
  • Receptors, Antigen, B-Cell