Expression of a B-cell-restricted isoform of CD45 is associated with maturity in rat serosal and connective-tissue mast cells.
Fas-associated protein with death domain/mediator of receptor induced toxicity (FADD/MORT1) was first described as a transducer of death receptor signalling but was later recognized also to be important for proliferation of T cells. B-cell lymphoma 3 (Bcl-3) is a relatively little understood member of the nuclear factor (NF)-kappaB family of transcription factors. We recently found that Bcl-3 is up-regulated in T cells from mice where FADD function is blocked by a dominant negative transgene (FADD-DN). To understand the importance of this, we generated FADD-DN/bcl-3(-/-) mice. Here, we report that T cells from these mice show massive cell death and severely reduced proliferation in response to T-cell receptor (TCR) stimulation in vitro. Transgenic coexpression of Bcl-2 (FADD-DN/bcl-3(-/-)/vav-bcl-2 mice) rescued the survival but not the proliferation of T cells. FADD-DN/bcl-3(-/-) mice had normal thymocyte numbers but reduced numbers of peripheral T cells despite an increase in cycling T cells in vivo. However, activation of the classical NF-kappaB and extracellular regulated kinase (ERK) pathways and expression of interleukin (IL)-2 mRNA upon stimulation were normal in T cells from FADD-DN/bcl-3(-/-) mice. These data suggest that FADD and Bcl-3 regulate separate pathways that both contribute to survival and proliferation in mouse T cells.
Yu
Chunping
C
Institute for Medical Microbiology, Technische Universität München, Munich, Germany.
Moghaddami
Mahin
M
Mayrhofer
Graham
G
D000818:Animals; D000937:Antigen-Antibody Reactions; D001169:Arthritis, Experimental / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D003239:Connective Tissue Cells; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008407:Mast Cells / Q000276:immunology*; D010529:Peritoneal Cavity / Q000166:cytology; D020033:Protein Isoforms / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012704:Serous Membrane / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D015415:Biomarkers; D020033:Protein Isoforms; D017493:Leukocyte Common Antigens