Open AccessEnhanced and accelerated lymphoproliferation in Fas-null mice.
Author(s) -
Masashi Adachi,
Sachiko Suematsu,
Takafumi Suda,
Daisuke Watanabe,
Hidehiro Fukuyama,
Jun Ogasawara,
Takashi Tanaka,
Nobuaki Yoshida,
Shinji Nagata
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.5.2131
Subject(s) - clonal deletion , superantigen , biology , cd8 , lymphocytosis , microbiology and biotechnology , antibody , null allele , fas receptor , apoptosis , immunology , lymphocyte , antigen , gene , mutant , t cell , immune system , t cell receptor , programmed cell death , genetics
Fas is a 45-kDa membrane protein that transduces an apoptotic signal. The mouse lymphoproliferation (lpr) mutation is a leaky mutation of Fas. In this study, we examined lymphocyte development in Fas-null mice generated by gene targeting. The Fas-/- mice progressively accumulated abnormal T cells (Thy1+, B220+, CD4-, and CD8-) and developed lymphadenopathy and splenomegaly, which were much more accelerated and pronounced than those in lpr mice. In addition, the Fas-null mice showed lymphocytosis, accompanied by lymphocytic infiltration in the lungs and liver. The number of apparently normal B cells also increased, and large amounts of immunoglobulins, including anti-DNA antibodies, were produced. Thymic clonal deletion, assessed by deletion of T cells reactive to mouse endogenous superantigens, was apparently normal in the Fas-/- mice, whereas the peripheral clonal deletion of mature T cells against a bacterial superantigen was impaired. These results suggested that Fas plays a decisive role in peripheral clonal deletion but not in negative selection in the thymus.