B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.
Int Immunol
; 25(4): 259-69, 2013 Apr.
Article
in En
| MEDLINE
| ID: mdl-23334952
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thymus Gland
/
Receptors, Antigen, T-Cell
/
T-Lymphocytes
/
T-Lymphocyte Subsets
/
Proto-Oncogene Proteins B-raf
Limits:
Animals
Language:
En
Journal:
Int Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2013
Document type:
Article
Affiliation country:
United States