DEVELOPMENT OF GRAFTED GLD CELLS IN ATHYMIC AND EUTHYMIC RECIPIENTS

Mice homozygous for the gld (generalized lymphoproliferative disease) and lpr (lymphoproliferation) mutations display similar autoimmune and lymphoproliferative diseases. Both result from defective apoptosis, t he targets of the lpr and gld mutations being the genes for, respectiv ely, an apoptosis-signalling receptor [the Fas antigen receptor (FasR) ] and its counter-receptor [the Fas ligand (FasL)]. Though this defini tely causes the development and accumulation of large numbers of unusu al Thy-1(+) B220(+) cells in peripheral lymphoid organs, details on ho w this actually occurs are still lacking. Whether differentiation of g ld T cells into Thy-1(+) B220(+) cells might depend on the environment was analysed by phenotyping the cells which expanded in four differen t immunodeficient environments (nubg, nulpr, scid and scinbg). Though all four types of congenic chimeras developed hyperglobulinaemia, auto immunity and a lymphoproliferative disease, substantial differences we re found for the athymic and euthymic chimeras. In the athymic gld chi meras, the lymphoproliferation concerned all cell subsets, whereas in the euthymic gld chimeras it was, as in gld mice, due to the accumulat ion of cells of the Thy-1(+) B220(+) subset. Thus, the gld T cells cou ld proliferate without differentiating into the Thy-1(+) B220(+) subse t, but this depended on the nature of the environment. Furthermore, em ergence of a gld syndrome in these four environments would suggest tha t B cells and stromal cells do not express Fast, at least in levels su fficient to compensate for the deficiency of the grafted gld cells.