Loss of Bim results in abnormal accumulation of mature CD4-CD8-CD44-CD25- thymocytes.
The process of thymopoiesis is tightly regulated by a series of selection events which ensure that only functional T-lymphocytes directed against foreign antigens are exported into the periphery. The adaptive immune response largely depends on the regulation of thymocyte development, and thymocytes which fail selection in the thymus are removed by apoptosis. However, the roles of specific apoptotic proteins in early T-lymphocyte development are poorly understood. Here, we report a novel function for Bim in thymocyte development. There is an accumulation of thymocytes in Bim(-/-) mice that lack expression of CD4, CD8, CD44, and CD25 but express CD3 and TCRbeta. Further, the CD4(-)CD8(-)CD25(-)CD44(-)CD3(+)TCRbeta(+) thymocytes are smaller and do not proliferate. These data suggest that these thymocytes are mature DN thymocytes that may have down-regulated the expression of CD4 and CD8. The DN thymocyte phenotype in Bim(-/-) mice is unaffected by the additional loss of Bak or Bax and is similar to the thymic phenotype in mice lacking both Bak and Bax. These data demonstrate that Bim functions to ensure the proper homeostasis of mature thymocytes during selection and thymic export.
Hutcheson
Jack
J
Department of Molecular Microbiology and Immunology, Saint Louis University, School of Medicine, 1402 South Grand Blvd, Saint Louis, MO 63104, USA.
Perlman
Harris
H
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D000072224:Bcl-2-Like Protein 11; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D038081:Organogenesis / Q000235:genetics / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000276:immunology; D051028:bcl-2-Associated X Protein / Q000276:immunology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D018960:Hyaluronan Receptors; D053645:Interleukin-2 Receptor alpha Subunit; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein