To determine the necessity for any individual BAFF receptor in the development of SLE.
Bcma, Taci, and Br3 null mutations were introgressed into NZM 2328 mice. NZM.Bcma−/−, NZM.Taci−/−, and NZM.Br3−/− mice were evaluated for lymphocyte phenotype and BAFF receptor expression by flow cytometry, B cell responsiveness to BAFF by in vitro culture, serum BAFF and total IgG and IgG anti-dsDNA levels by ELISA, renal immunopathology by immunofluorescence and histopathology, and clinical disease.
NZM.Bcma−/−, NZM.Taci−/−, and NZM.Br3−/− mice failed to surface-express BCMA, TACI, and BR3, respectively. Transitional and follicular B cells from NZM.Br3−/− mice were much less responsive to BAFF than the corresponding cells from wild-type (WT), NZM.Bcma−/−, or NZM.Taci−/− mice. In comparison to WT mice, NZM.Bcma−/− and NZM.Taci−/− mice harbored increased spleen B cells, T cells, and plasma cells (PC), whereas serum total IgG and IgG anti-dsDNA levels were similar. Despite their paucity of B cells, NZM.Br3−/− mice harbored increased T cells and WT-like numbers of PC and levels of IgG anti-dsDNA. Serum BAFF levels were increased in NZM.Taci−/− and NZM.Br3−/− mice but were decreased in NZM.Bcma−/− mice. Despite their phenotypic differences, renal immunopathology and clinical disease in NZM.Bcma−/−, NZM.Taci−/−, and NZM.Br3−/− mice were at least as severe as in WT mice.
Any single BAFF receptor, including BR3, is dispensable to development of SLE in NZM mice. Development of disease in NZM.Br3−/− mice demonstrates that BAFF/BCMA and/or BAFF/TACI interactions contribute to SLE and that profound, life-long reduction in B cells does not guarantee protection from SLE.