CONVENTIONAL B-CELLS, NOT B1 CELLS, ARE THE SOURCE OF AUTOANTIBODIES IN CHRONIC GRAFT-VERSUS-HOST DISEASE

B1 (CD5+) B cells have been implicated as a source of certain autoanti bodies in several murine and human studies. We have previously shown i n the lpr model of autoimmunity, however, that conventional B cells, n ot B1 cells, were the source of autoantibodies directed at chromatin, ssDNA, and IgG. In the current study, we have investigated the origin of autoantibodies in chronic graft-versus-host (GVH) disease, induced in nonautoimmune mice by transferring Ia-incompatible spleen cells. GV H mice develop multiple autoantibodies and significant kidney damage. Therefore, this model allowed us to examine the B cell subset involved in both autoantibody production and tissue injury. We used two protoc ols to establish B cell chimeras that possessed immunoglobulin heavy c hain (Igh) allotype-marked peritoneal (B1-cell source) cells and bone marrow-derived (conventional B cell source) cells from nonautoimmune C 57BL/6kh (B6) congenic mice. In both types of chimeras, chronic GVH wa s induced by giving mice alloreactive T cells i.p. All of the subseque nt anti-chromatin, RF, and anti-ssDNA autoantibodies were produced by the conventional B cells and not by B1 cells. In addition, glomerular immune complex deposits of both IgM and IgG originated from the conven tional B cells and not from B1 cells. These findings thus parallel tho se from our previous work on autoantibodies in lpr, and extend those f indings by demonstrating that antibodies within pathogenic immune comp lexes in the kidneys are also exclusively of conventional B cell origi n.