IgD can largely substitute for loss of IgM function in B cells.
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.
Lutz
C
C
Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Ledermann
B
B
Kosco-Vilbois
M H
MH
Ochsenbein
A F
AF
Zinkernagel
R M
RM
Köhler
G
G
Brombacher
F
F
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology; D007072:Immunoglobulin D / Q000502:physiology*; D007075:Immunoglobulin M / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D010529:Peritoneal Cavity / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013234:Stem Cells; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell