title: Murine B cell development and antibody responses to model antigens are not impaired in the absence of the TNF receptor GITR.
abstract: The Glucocorticoid-Induced Tumor necrosis factor Receptor GITR, a member of the tumor necrosis factor receptor superfamily, has been shown to be important in modulating immune responses in the context of T cell immunity. B lymphocytes also express GITR, but a role of GITR in humoral immunity has not been fully explored. To address this question, we performed studies to determine the kinetics of GITR expression on naïve and stimulated B cells and the capacity of B cells to develop and mount antibody responses in GITR(-/-) mice. Results of our studies indicate that all mature B cells express GITR on the cell surface, albeit at different levels. Expression of GITR on naïve mature B cells is upregulated by BCR signaling, but is counteracted by helper T cell-related factors and other inflammatory signals in vitro. In line with these findings, expression of GITR on germinal center and memory B cells is lower than that on naïve B cells. However, the expression of GITR is strongly upregulated in plasma cells. Despite these differences in GITR expression, the absence of GITR has no effect on T cell-dependent and T cell-independent antibody responses to model antigens in GITR(-/-) mice, or on B cell activation and proliferation in vitro. GITR deficiency manifests only with a slight reduction of mature B cell numbers and increased turnover of naïve B cells, suggesting that GITR slightly contributes to mature B cell homeostasis. Overall, our data indicate that GITR does not play a significant role in B cell development and antibody responses to T-dependent and independent model antigens within the context of a GITR-deficient genetic background.
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver School of Medicine, Denver, Colorado, United States of America.
authors.forename: Lenka Sinik
authors.initials: LS
authors.lastname: Teodorovic
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
authors.forename: Roberta
authors.initials: R
authors.lastname: Pelanda
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D053450:Glucocorticoid-Induced TNFR-Related Protein