title: T cell-mediated activation and regulation of anti-chromatin B cells.
abstract: We have taken an immunoglobulin transgenic approach to study how self-reactive B cells are held in check in healthy mice and what parameters contribute to their activation in autoimmunity. Using this strategy, we have documented that a population of anti-chromatin B cells migrate to the periphery. In a healthy background, these cells have a reduced lifespan, appear developmentally arrested, and localize primarily to the T/B cell interface in the spleen. Importantly, they are capable of differentiating into antibody-forming cells when provided with T cell help. T(H)1 and T(H)2 cells induce IgG2a and IgG1 autoantibodies, respectively. In the context of the autoimmune-prone lpr/lpr or gld/gld mutations, these autoreactive B cells populate the B cell follicle, and this is dependent upon CD4 T cells. However, after 10 weeks of age serum autoantibodies are produced. We hypothesize that control of autoantibody production in young autoimmune-prone mice is regulated by the counterbalancing influence of regulatory T cells. We show that while autoantibody production is blocked in the context of regulatory T cells, early events characterizing a productive T cell-B cell interaction are not disturbed, with the notable exceptions of T(H) ICOS levels and IFN-gamma and IL-10 production.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, United States.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pagán
authors.forename: Hilda E
authors.initials: HE
authors.lastname: Ramón
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hondowicz
authors.forename: Jan
authors.initials: J
authors.lastname: Erikson
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002843:Chromatin / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D001323:Autoantibodies; D002843:Chromatin