Diseases caused by reactions of T lymphocytes to incompatible structures of the major histocompatibility complex. II. Autoantibodies deposited along the basement membrane of skin and their relationship to immune-complex glomerulonephritis
van Elven, E.H.; Agterberg, J.; Sadal, S.; Gleichmann, E.
Journal of Immunology 126(5): 1684-1691
1981
ISSN/ISBN: 0022-1767 PMID: 7012237 Document Number: 172742
The in vivo deposition of autoantibodies along the basement membrane of skin (BMS) in nonirradiated (C57BL/10 .times. DBA/2)F1 hybrid mice undergoing a chronic graft-vs.-host reaction (GVHR) was studied. The formation of these antibodies required T lymphocytes in the inoculum of DBA/2 donor cells and an H-2 incompatibility in the recipients. The possibility that the antibodies were anti-F1 alloantibodies, produced by DBA/2 B cells, was ruled out by the finding that they were deposited to the same extent in the native (F1) skin of GVH F1 mice and in DBA/2 skin grafted to GVH F1 mice. IgG1 and IgA antibodies and complement, fixed in vivo in a linear fashion along the BMS, were demonstrable by the immunofluorescence technique (IFT) and by immuno-electron-microscopy. Antibodies reacting to the BMS were not demonstrable in the sera of GVH F1 mice having such antibodies fixed in vivo. The antibodies fixed in vivo were eluted from the BMS by applying 2 M KNCS. By indirect IFT (IIFT) the eluted antibodies bound to the BMS and esophageal BM but not to the glomerular BM; this staining pattern was found irrespective of whether the tissues tested were taken from noninjected F1 (N F1) or from DBA/2 mice. In addition to antibodies deposited along the BMS, the skin eluate contained antinuclear antibodies. These antibodies, but not those binding along the BMS, could be absorbed from the eluate by nuclei of chicken erythrocytes. Although containing antinuclear antibodies, the skin eluate did not possess detectable antibody activity against the double-stranded DNA of Crithidia luciliae. It could not be decided whether the antibody activity in the skin eluate was due to genuine anti-BMS antibodies or to immune complexes with a predilection for the subepidermal zone. The in vivo deposition of IgG antibodies along the BMS of F1 mice correlated well with the development of a severe nephrotic syndrome due to immune-complex glomerulonephritis in these mice. Parallels between autoantibody formation induced by the GVHR and that occurring spontaneously in systemic lupus erythematosus are discussed.