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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.

SUBMITTER: Dillon TJ 

PROVIDER: S-EPMC3597848 | biostudies-other | 2013 Apr

REPOSITORIES: biostudies-other

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B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.

Dillon Tara J TJ   Takahashi Maho M   Li Yanping Y   Tavisala Srilatha S   Murray Susan E SE   Moran Amy E AE   Parker David C DC   Stork Philip J S PJ  

International immunology 20130118 4

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  ...[more]