title: Inhibition of B-cell death does not restore T-cell-dependent immune responses in CD40-deficient mice.
abstract: Signalling through CD40 is essential for the development of immunoglobulin G (IgG) antibody responses, germinal centres and B-cell memory against T-dependent antigens. In addition, engagement of CD40 in B cells promotes cell survival by inducing the expression of anti-apoptotic members of the bcl-2 family of cell-death regulators. In the present study we analysed whether T-dependent immune responses can be developed in mice deficient in CD40 if the anti-apoptotic activity mediated by the engagement of CD40 in B cells is compensated by the constitutive over-expression of anti-apoptotic genes of the bcl-2 family. We showed that the over-expression of either hbcl-2 or hbcl-xL transgenes in B cells is not sufficient to restore IgG antibody responses and germinal centre formation in CD40-deficient mice. These results indicate that CD40 functions, other than those mediated through survival, are required for the establishment of T-dependent B-cell responses.
authors.affiliation: Laboratory of Immunology, Department of Molecular Biology, (Unit associated with CIB/CSIC), University of Cantabria, Santander, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Merino
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Díez
authors.forename: María
authors.initials: M
authors.lastname: Muñiz
authors.forename: Luis
authors.initials: L
authors.lastname: Buelta
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Marcos
authors.initials: M
authors.lastname: López-Hoyos
authors.forename: Ramón
authors.initials: R
authors.lastname: Merino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D019254:Genes, bcl-2 / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051020:bcl-X Protein
chemical_list: C494812:Bcl2l1 protein, mouse; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein