BAFF overexpression promotes anti-dsDNA B-cell maturation and antibody secretion.
Overexpression of BAFF is believed to play an important role in systemic lupus erythematosus and elevated levels of serum BAFF have been found in lupus patients. Excess BAFF also leads to overproduction of anti-dsDNA antibodies and a lupus-like syndrome in mice. In the present study, we use mice transgenic for the R4A-Cmu (IgM) heavy chain of an anti-dsDNA antibody, to study the effects of BAFF overexpression on anti-dsDNA B-cell regulation. We observe that overexpression of BAFF promotes anti-dsDNA B-cell maturation and secretion of antibody and enriches for transgenic anti-dsDNA B cells in the marginal zone and follicular splenic compartments. In addition, our data suggests that BAFF rescues a subset of anti-dsDNA B cells from a regulatory checkpoint in the transitional stage of development.
Thorn
Mitchell
M
Department of Biology, The City College of New York, 138th Street, Convent Avenue, New York, NY 10031, United States.
Lewis
Rita H
RH
Mumbey-Wafula
Alice
A
Kantrowitz
Stefan
S
Spatz
Linda A
LA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D004247:DNA / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D000974:Antibodies, Antinuclear; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D004247:DNA