title: Mechanisms by Which B Cells and Regulatory T Cells Influence Development of Murine Organ-Specific Autoimmune Diseases.
abstract: Experiments with B cell-deficient (B-/-) mice indicate that a number of autoimmune diseases require B cells in addition to T cells for their development. Using B-/- Non-obese diabetic (NOD) and NOD.H-2h4 mice, we demonstrated that development of spontaneous autoimmune thyroiditis (SAT), Sjogren's syndrome and diabetes do not develop in B-/- mice, whereas all three diseases develop in B cell-positive wild-type (WT) mice. B cells are required early in life, since reconstitution of adult mice with B cells or autoantibodies did not restore their ability to develop disease. B cells function as important antigen presenting cells (APC) to initiate activation of autoreactive CD4+ effector T cells. If B cells are absent or greatly reduced in number, other APC will present the antigen, such that Treg are preferentially activated and effector T cells are not activated. In these situations, B-/- or B cell-depleted mice develop the autoimmune disease when T regulatory cells (Treg) are transiently depleted. This review focuses on how B cells influence Treg activation and function, and briefly considers factors that influence the effectiveness of B cell depletion for treatment of autoimmune diseases.
authors.affiliation: Department of Surgery, University of Missouri, Columbia, MO 65212, USA. ellisj@health.missouri.edu.|Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO 65212, USA. ellisj@health.missouri.edu.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO 65212, USA. mullenh@health.missouri.edu.|Department of Medicine, University of Missouri, Columbia, MO 65212, USA. mullenh@health.missouri.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
keywords: APC; B cells; autoimmunity; effector T cells; regulatory T cells