UP-REGULATION OF FAS AND THE COSTIMULATORY MOLECULES B7-1 AND B7-2 ONPERIPHERAL LYMPHOCYTES IN AUTOIMMUNE B6 GLD MICE/

C57BL/gld/gld (B6/gld) mice have a point mutation in the gene for Fas ligand (FasL) resulting in nonfunctional Fast protein, We hypothesized that the lack of normal Fas/FasL interactions in these mice might res ult in abnormalities of Fas expression, Thus, we compared spleen cells from B6/gld mice and normal B6 control mice, While B6 spleen cells co nsisted of two main populations, Fas(high) (high Fas expression) and F as(low) (low Fas expression), nearly all B6/gld spleen cells were Fas( high), Two-color immunofluorescence revealed that the Fas(high) and Fa s(low) populations in the B6 spleen were Thy-1.2(+) (T cells) and IgM( +) (B cells), respectively, whereas both T cells and B cells in the B6 /gld spleen were Fas(high), indicating that Fas expression is increase d on B cells in the B6/gld spleen, This phenomenon was age related and restricted to peripheral lymphocytes. In addition to Fas, B6/gld sple nic B cells showed increased expression of the costimulatory molecule B7-2, while the related costimulatory molecule B7-1 was up-regulated o n both B cells and T cells in the B6/gld spleen, In vitro, both B cell s and T cells from the B6/gld spleen showed an increase in susceptibil ity to apoptosis mediated by soluble anti-fas Ab, These results sugges t that some lymphocytes in B6/gld mice are primed to undergo Fas-media ted apoptosis, but are unable to do so due to the absence of functiona l Fast. Further study of such abnormal lymphocytes in the B6/gld splee n may elucidate the nature of autoimmunity in these mice.