Systemic lupus erythematosus (SLE), in mice as in humans, is characterized by a wide spectrum of autoantibodies mainly directed at cellular antigens (1, 2). T cells are apparently required for the induction of such autoantibodies, but their exact role in spontaneous disease remains to be defined (3, 4). In chronic graft-versus-host (GVH)'disease, an SLE-like syndrome can be induced in normal mice by transfer ofallogeneic Tcells. It is thought that the allohelper Tcells ofthe donor react against incompatible la structures of the host and generate excessive help, which activates a subpopulation of B cells in the host that is selfreactive (5-7). Such a GVH reaction occurs between B6 (or its Igh allotype congenic strain B6. C20) and bm12 mice through the recognition of the mutant bm12 Ia by the B6 (or B6. C20) cells, and vice versa (6; and Morris, SC, P L. Cohen, and RA Eisenberg, manuscript submitted for publication). A syndrome that closely resembles SLE is induced, with autoantibodies to erythrocytes, chromatin, nuclear antigens, and to a more limited degree, double-stranded DNA.

Activation of resting B cells to proliferate and differentiate into antibody-producing cells occurs through the binding of antigen by the B cell surface Ig receptor and the participation of T cell help. Previous studies have established that Th cells can support antigen-specific B cell responses through two distinct pathways (8-13). Cognate help results from direct TB contact, while noncognate or bystander help is mediated through factors released from activated T cells that can act at a distance upon antigen-activated B cells. Since chronic GVH results from the stimulation of alloreactive T helper cells (14), and their inappropriate collaboration with the host B cells (5, 15), we investigated whether the donor Tcells recognized foreign la directly on the B cell stimulated to make autoantibodies. Double-congenic chimeras, containing two sets of B cells that differed at both Ia and Igh allotype, were used to determine whether the autoantibody forming cells were specifically stimulated by the autoreactive T cells and/or if a bystander effect was occurring. The isotype and allotype ofthe Coombs antibodies were determined, as was the allotype ofthe IgG2a