The RAG recombinase dictates functional heterogeneity and cellular fitness in natural killer cells.
Cell
; 159(1): 94-107, 2014 Sep 25.
Article
in En
| MEDLINE
| ID: mdl-25259923
ABSTRACT
The emergence of recombination-activating genes (RAGs) in jawed vertebrates endowed adaptive immune cells with the ability to assemble a diverse set of antigen receptor genes. In contrast, innate lymphocytes, such as natural killer (NK) cells, are not believed to require RAGs. Here, we report that NK cells unable to express RAGs or RAG endonuclease activity during ontogeny exhibit a cell-intrinsic hyperresponsiveness but a diminished capacity to survive following virus-driven proliferation, a reduced expression of DNA damage response mediators, and defects in the repair of DNA breaks. Evidence for this novel function of RAG has also been observed in T cells and innate lymphoid cells (ILCs), revealing an unexpected role for RAG proteins beyond V(D)J recombination. We propose that DNA cleavage events mediated by RAG endow developing adaptive and innate lymphocytes with a cellular "fitness" that safeguards their persistence later in life during episodes of rapid proliferation or cellular stress.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Homeodomain Proteins
/
DNA-Binding Proteins
Limits:
Animals
Language:
En
Journal:
Cell
Year:
2014
Type:
Article
Affiliation country:
United States