title: Expression of CD80/86 on B cells is essential for autoreactive T cell activation and the development of arthritis.
abstract: Depletion of B cells in rheumatoid arthritis is therapeutically efficacious. Yet, the mechanism by which B cells participate in the inflammatory process is unclear. We previously demonstrated that Ag-specific B cells have two important functions in the development of arthritis in a murine model of rheumatoid arthritis, proteoglycan (PG)-induced arthritis (PGIA). PG-specific B cells function as autoantibody-producing cells and as APCs that activate PG-specific T cells. Moreover, the costimulatory molecule CD86 is up-regulated on PG-specific B cells in response to stimulation with PG. To address the requirement for CD80/CD86 expression on B cells in the development of PGIA, we generated mixed bone marrow chimeras in which CD80/CD86 is specifically deleted on B cells and not on other APC populations. Chimeras with a specific deficiency in CD80/CD86 expression on B cells are resistant to the induction of PGIA. The concentration of PG-specific autoantibody is similar in mice sufficient or deficient for CD80/86-expressing B cells, which indicates that resistance to PGIA is not due to the suppression of PG-specific autoantibody production. CD80/86-deficient B cells failed to effectively activate PG-specific autoreactive T cells as indicated by the failure of T cells from PG-immunized CD80/86-deficient B cell chimeras to transfer arthritis into SCID mice. In vitro secondary recall responses to PG are also dependent on CD80/86-expressing B cells. These results demonstrate that a CD80/86:CD28 costimulatory interaction between B cells and T cells is required for autoreactive T cell activation and the induction of arthritis but not for B cell autoantibody production.
authors.affiliation: Department of Immunology/Microbiology, Rush University, Medical Center, Chicago, IL 60612, USA.
authors.forename: Shannon K
authors.initials: SK
authors.lastname: O'Neill
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Cao
authors.forename: Keith M
authors.initials: KM
authors.lastname: Hamel
authors.forename: Paul D
authors.initials: PD
authors.lastname: Doodes
authors.forename: Gabor
authors.initials: G
authors.lastname: Hutas
authors.forename: Alison
authors.initials: A
authors.lastname: Finnegan
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051940:B7-2 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D011509:Proteoglycans / Q000008:administration & dosage / Q000276:immunology; D011828:Radiation Chimera; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D011509:Proteoglycans