Up-regulation of Fas and the costimulatory molecules B7-1 and B7-2 on peripheral lymphocytes in autoimmune B6/gld mice.
C57BL/6-gld/gld (B6/gld) mice have a point mutation in the gene for Fas ligand (FasL) resulting in nonfunctional FasL protein. We hypothesized that the lack of normal Fas/FasL interactions in these mice might result in abnormalities of Fas expression. Thus, we compared spleen cells from B6/gld mice and normal B6 control mice. While B6 spleen cells consisted of two main populations, Fashigh (high Fas expression) and Faslow (low Fas expression), nearly all B6/gld spleen cells were Fashigh. Two-color immunofluorescence revealed that the Fashigh and Faslow 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 Fashigh, indicating that Fas expression is increased on B cells in the B6/gld spleen. This phenomenon was age related and restricted to peripheral lymphocytes. In addition to Fas, B6/gld splenic B cells showed increased expression of the costimulatory molecule B7-2, while the related costimulatory molecule B7-1 was up-regulated on both B cells and T cells in the B6/gld spleen. In vitro, both B cells and T cells from the B6/gld spleen showed an increase in susceptibility to apoptosis mediated by soluble anti-Fas Ab. These results suggest that some lymphocytes in B6/gld mice are primed to undergo Fas-mediated apoptosis, but are unable to do so due to the absence of functional FasL. Further study of such abnormal lymphocytes in the B6/gld spleen may elucidate the nature of autoimmunity in these mice.
Weintraub
J P
JP
Department of Medicine, University of North Carolina, Chapel Hill 27599, USA.
Eisenberg
R A
RA
Cohen
P L
PL
D000367:Age Factors; D000818:Animals; D000906:Antibodies / Q000502:physiology; D015703:Antigens, CD / Q000096:biosynthesis*; D017209:Apoptosis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D001854:Bone Marrow Cells; D007072:Immunoglobulin D / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D013154:Spleen / Q000166:cytology; D015854:Up-Regulation / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis* / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D019014:fas Receptor