title: The absence of immunoglobulin D B cell receptor-mediated signals promotes the production of autoantibodies and exacerbates glomerulonephritis in murine lupus.
abstract: Immunoglobulin (Ig)D is the major antigen receptor isotype co-expressed with IgM on the surface of most peripheral B cells in mice and humans. However, the biological role of IgD as B cell receptor (BCR) has remained unclear. Previous studies have indicated that IgD may play a role in B cell tolerance. To understand the role of IgD in B cell tolerance and autoimmunity, we have examined the development of autoimmune syndrome in lpr mice deficient for IgD. The present study showed that IgD deficiency did not alter lymphoproliferation and lymphocyte activation in lpr mice. The survival and proliferation of B cells were not affected by the absence of IgD, indicating that IgD BCR-mediated signals do not have an important role in negative selection of autoreactive B cell clones. Interestingly, compared to IgD-competent littermates, lpr mice with IgD deficiency had elevated autoantibody production, increased deposition of immune complex in the kidney and more severe nephritis. Accumulation of abnormal CD4(-) CD8(-) αβ(+) T cells was accelerated in IgD(-/-) lpr mice compared to lpr mice. These results suggest that IgD BCR-mediated signals may be involved in the differentiation of autoreactive B cells into plasma cells and abnormal T cell expansion.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Tian
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.forename: S
authors.initials: S
authors.lastname: Han
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity / Q000276:immunology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D018450:Disease Progression; D004406:Dysgammaglobulinemia / Q000150:complications / Q000276:immunology*; D007072:Immunoglobulin D / Q000172:deficiency*; D008181:Lupus Nephritis / Q000150:complications / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D018448:Models, Immunological; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007072:Immunoglobulin D; D011947:Receptors, Antigen, B-Cell