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 autoantibodies in several murine and human studies. We have previously shown in the lpr model of autoimmunity, however, that conventional B cells, not 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 la-incompatible spleen cells. GVH 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 protocols to establish B cell chimeras that possessed immunoglobulin heavy chain (lgh) allotype-marked peritoneal (B1-cell source) cells and bone marrow-derived (conventional B cell source) cells from nonautoimmune C57BL/6kh (B6) congenic mice. In both types of chimera, chronic GVH was induced by giving mice alloreactive T cells i.p. All of the subsequent 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 conventional B cells and not from B1 cells. These findings thus parallel those from our previous work on autoantibodies in lpr, and extend those findings by demonstrating that antibodies within pathogenic immune complexes in the kidneys are also exclusively of conventional B cell origin.
Reap
E A
EA
Department of Medicine, University of North Carolina, Chapel Hill 27599-7280.
Sobel
E S
ES
Jennette
J C
JC
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology; D018956:CD5 Antigens; D002678:Chimera; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology / Q000637:transplantation
D015703:Antigens, CD; D001323:Autoantibodies; D018956:CD5 Antigens