scholarly journals GRAFT-VERSUS-HOST REACTION ACROSS DIFFERENT REGIONS OF THE H-2 COMPLEX OF THE MOUSE

1973 ◽  
Vol 137 (5) ◽  
pp. 1213-1225 ◽  
Author(s):  
Jan Klein ◽  
Jong M. Park

H-2 crossovers and their parental strains were arranged into 35 combinations in which the adult donor of spleen cells differed from the newborn recipient in the whole H-2 complex, or in three, two, or one region of the complex. A Simonsen splenomegaly assay was then used to test the contribution of the individual H-2 regions to the graft-versus-host reaction (GVHR). It was shown that the strongest GVHR was associated with the Ir region. Differences in the Ir region caused significant splenomegaly in spite of the fact that no antigens detectable by conventional serological methods have thus far been associated with this region. Differences in the K and D regions showed only a borderline effect on GVHR in spite of the fact that these regions code for most, if not all, of the antigens detectable by conventional serological and transplantation methods. The K region alone caused no stronger GVHR than the D legion alone; however, K + Ir region differences led to much stronger GVHR than D region differences. The Ss-Slp region also showed only a borderline effect on GVHR. Differences in two or more H-2 regions usually caused greater splenomegaly than differences in each of the regions separately. On the basis of these findings it is concluded that the strongest GVHR is caused by genes distinct from the known histocompatibility genes of the H-2 complex. It is speculated that the GVHR genes are identical with the mixed lymphocyte reaction (MLR) and Ir genes and that the product of these genes are receptors on the surface of the thymus-derived lymphocytes (T cells).

1990 ◽  
Vol 171 (2) ◽  
pp. 503-517 ◽  
Author(s):  
S C Morris ◽  
R L Cheek ◽  
P L Cohen ◽  
R A Eisenberg

A chronic graft-versus-host reaction (GVH) induced in nonautoimmune mice causes a syndrome that closely resembles SLE. In this model, donor T cells react against incompatible host Ia structures and generate excessive help, which activates a subpopulation of self-reactive B cells. We have studied whether these self-reactive B cells are activated by direct interaction with alloreactive T cells or by nonspecific bystander effects. Two types of chimeras were made: double-parental chimeras, differing at both Ia and Igh allotype [B6.C20 + bm12----(B6.C20 x bm12)F1]; and control chimeras [(B6.C20 x bm12)F1----(B6.C20 x bm12)F1]. A chronic GVH syndrome was induced in the chimeras by infusion of B6 or bm12 spleen cells. Coombs and antichromatin autoantibodies were measured using Igh allotype-specific immunoassays. The double-parental chimeras that received bm12 cells made autoantibodies principally of the Igha allotype, indicating that the bm12 T cells interacted only with the Iab-bearing host B cells. Conversely, double-parental chimeras that received B6 cells made mostly Ighb autoantibodies, indicating direct cognate interaction with the Iabm12-bearing host B cells. The control chimeras made autoantibodies of both allotypes. These results indicate that autoantibodies in chronic GVH result from direct T-B interactions and not from nonspecific T cell-derived factors.


Dermatology ◽  
1984 ◽  
Vol 169 (2) ◽  
pp. 76-79 ◽  
Author(s):  
Michael David ◽  
Batya Shohat ◽  
Gregory Morozinski ◽  
Eleasar J. Feuerman

2006 ◽  
Vol 203 (7) ◽  
pp. 1761-1772 ◽  
Author(s):  
Esther J. Witsch ◽  
Hong Cao ◽  
Hidehiro Fukuyama ◽  
Martin Weigert

The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4+ T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and β-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with “editor” L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress κ and λ L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.


Development ◽  
1961 ◽  
Vol 9 (3) ◽  
pp. 355-369
Author(s):  
J. B. Solomon

When implants of spleen from mature homologous chicken are placed on the chorio-allantoic membranes of chicken eggs, certain of the adult cells rapidly invade the vascular system of the host (Dantchakoff, 1918). Some of these cells colonize the spleen of the host embryo (Biggs & Payne, 1959; Ebert, 1959; Simonsen, 1957) and after a short latent period these adult cells proliferate in the host spleen under the stimulus of continuous exposure to the individual specific foreign antigens of the host. The resulting splenomegaly of the host embryo is generally recognized to be due to the proliferation of these immunologically competent cells. However, the possibility of enhanced mitotic division of spleen cells of the embryonic host being also partly responsible for the splenomegaly has been suggested by Biggs & Payne (1959). This type of transplantation effect has been termed the ‘graft versus host’ reaction (Simonsen, 1957) of which the initial symptoms are splenomegaly and hepatomegaly of the host.


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