DIFFERENTIAL REQUIREMENT FOR AUTOANTIBODY-PRODUCING B-CELLS FOR INDUCTION OF LYMPHOCYTIC VERSUS GRANULOMATOUS EXPERIMENTAL AUTOIMMUNE-THYROIDITIS

Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro w ith MTG transfer experimental autoimmune thyroiditis (EAT) in which th e thyroid cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Addition of anti-IL2R antibody to cultures with MTg leads to activation of cells that induce granulomatous EAT, accompani ed by high serum anti-MTg autoantibody responses, in recipient mice. C D4+ T cells are required to induce both forms of EAT; whether B cells and/or autoantibodies produced by MTg-sensitized B cells also contribu te to disease severity or the type of thyroid histopathology is unknow n. in our study, B cells and autoantibody responses produced in recipi ent mice were reduced either by column removal of B cells from donor s pleen cells or by treatment of recipient mice with anti-I-A(K) mAb at the time of cell transfer. These maneuvers only slightly reduced the s everity of lymphocytic EAT but markedly reduced the severity and incid ence of granulomatous EAT developing in recipient mice. Delaying the i nitiation of anti-I-A(K) treatment until 6 days after cell transfer wa s less effective in reducing anti-MTg autoantibody responses or granul omatous EAT. These studies all suggested that anti-MTg autoantibodies were required for development of granulomatous but not lymphocytic EAT . However anti-I-A(K)-treated recipients receiving injections of anti- MTg antibody or having serum antibody induced by prior immunization wi th MTg and LPS also developed less severe granulomatous EAT than contr ols. These results suggest that sensitized CD4+ T cells and circulatin g anti-MTg autoantibody are not sufficient for development of granulom atous thyroid lesions. It is possible that antibodies having a unique function or specificity are produced in mice developing granulomatous EAT or thyroid-infiltrating B cells may directly contribute to the gra nulomatous inflammatory response.