SELF-REACTIVE B-CELLS ARE NOT ELIMINATED OR INACTIVATED BY AUTOANTIGEN EXPRESSED ON THYROID EPITHELIAL-CELLS

Graves' Disease results from the production of autoantibodies against receptors for thyroid stimulating hormone (TSH) on thyroid epithelial cells, and represents the prototype for numerous autoimmune diseases c aused by autoantibodies that bind to organ-specific cell memb brane an tigens. To study how humoral tolerance is normally maintained to membr ane antigens, transgenic mice were generated selectively expressing me mbrane-bound hen egg lysozyme (mHEL) on the thyroid epithelium. In con trast to the deletion of autoreactive B cells triggered by systemic mH EL (Hartley, S.B., J. Crosbie, R. Brink, A.B. Kantor, A. Basten, and C .C. Goodnow. 1991. Nature. 353:765-769), selective expression of mHEL autoantigen on thyroid cells did not trigger elimination or inactivati on of circulating HEL-reactive B cells. These results provide evidence that tolerance is not actively acquired to organ-specific antigens in the preimmune B cell repertoire, underscoring the importance of maint aining tolerance to such antigens by other mechanisms. The role of an intact endothelial barrier in sequestering organ-specific antigens fro m circulating preimmune B cells is discussed.