2, N ~ 1, and identification of a 85KD cell surface molecule that is accumulated in the pericellular
- G. R. Burmester, D. Menche, P. Merryman, A. Dimitriu-Bona, R M. Klein, Winchester
- Clinical rheumatology,
A chronic graft-versus-host reaction (GVHR) was induced in adult nonirradiated (B10 x DBA/2)F 1 mice by I.V. injection of live DBA/2 (H-2 d/d) lymphocytes. Although both a class I (K/D) and a class II (I-A/I-E) incompatibility existed in the F l recipients, DBA/2 donor cells were unable to induce the severe lympho-hemopoietic depletion characteristic of acute GVHD; in this DBA/2 differs from most other strains of mice, such as B10 and B6. Instead, DBA/2 cells induced an SLE-like GVHD which included the following symptoms: 1) autoantibodies to thymocytes, erythrocytes, nuclear antigens, dsDNA, and other less well-defined self-antigens ; 2) increased serum titers of antibodies to the surface antigen (gp70) of endogenous murine leukemia viruses; 3) a 10to 50-fold increase in spontaneous lgG formation and a 4-fold increase in IgM formation in the spleen, these were accompanied by hyper7-globulinemia; 4) a ubiquitous periarteritis; 5) the deposition of IgG and IgM antibodies along the basement membrane of the skin; and 6) a severe immune-complex glomerulonephritis ; significant amounts of anti-gp70 antibodies and antinuclear antibodies were eluted from diseased kidneys. In spite of the tremendous increase in spontaneous Ig production and the spontaneous formation of very high titers of SLE-like autoantibodies, however, we failed to detect a spontaneous formation of antibodies to non-self, such as SRBC, HRBC, TNP, levan, bacteriophage fd, and plasmodium berghei. Upon planned immunization with SRBC, the specific antibody response of SLE-like GVH mice was even decreased. Interestingly, there was no autoantibody formation to organ-specific antigens, such as thyroglobulin. Thus, the increased antibody formation in these SLE-like GVH mice was preferntiaUy, if not exclusively, directed against self-antigens involved in SLE. We propose that due to their intrinsic structure these self-antigens are more apt than others to trigger the corresponding autoreactive B cells in the presence of unspecific T cell help.