title: B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.
abstract: The duration of signaling through the MAP kinase (or ERK pathway) cascade has been implicated in thymic development, particularly positive and negative selection. In T cells, two isoforms of the MAP kinase kinase kinase Raf function to transmit signals from the T-cell receptor to ERK: C-Raf and B-Raf. In this study, we conditionally ablated B-Raf expression within thymocytes to assess the effects on ERK activation and thymocyte development. The complete loss of B-Raf is accompanied by a dramatic loss of ERK activation in both the double positive (DP) and single positive (SP) thymocytes, as well as peripheral splenocytes. There was a significant decrease in the cellularity of KO thymi, largely due to a loss of pre-selected DP cells, a decrease in DP cells undergoing positive selection, and a defect in SP maturation. B-Raf plays significant roles in survival of DP thymocytes and function of SP cells in the periphery. Surprisingly, we saw no effect of B-Raf deficiency on negative selection of autoreactive SP thymocytes, despite the greatly reduced ERK activation in these cells.
authors: Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
authors: Tara J
authors: TJ
authors: Dillon
authors: Maho
authors: M
authors: Takahashi
authors: Yanping
authors: Y
authors: Li
authors: Srilatha
authors: S
authors: Tavisala
authors: Susan E
authors: SE
authors: Murray
authors: Amy E
authors: AE
authors: Moran
authors: David C
authors: DC
authors: Parker
authors: Philip J S
authors: PJ
authors: Stork
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases