Rheumatoid factor B cell tolerance via autonomous Fas/FasL-independent apoptosis

Normal individuals do not express the high-affinity autoantibodies specific for self-IgG (rheumatoid factors, RF) that are commonly seen in rheumatoid arthritis patients. Studies of transgenic mice expressing a human IgM rheu matoid factor have shown that one mechanism by which higher affinity RF B c ells are tolerized to IgG is through abortive RF B cell activation followed by deletion in the absence of T cell help. We show that RF B cell deletion occurs through an intrinsic apoptotic mechanism that is independent of the Fas/FasL pathway and does not involve active killing by T cells, as it occ urs in RAG-1-deficient RF transgenic mice to the same extent as in the pare ntal RF transgenic line. (C) 1999 Academic Press.