Natural killer (NK) cells are innate lymphocytes that have features of adaptive immune cells, such as clonal proliferation and the generation of memory-like cells in response to infection. In C57BL/6 mice, recognition of the mouse cytomegalovirus (MCMV)-encoded glycoprotein m157 by the NK cell-activating receptor LY49H induces a proliferative 'burst' and an effector response that protects against infection. A new study shows that the zinc finger and BTB domain-containing transcription factor ZBTB32 is required for this protective response. Indeed, transfer of Zbtb32−/− LY49H+ NK cells to neonate mice (which lack mature B, T and NK cells) rescued one-third of mice from otherwise lethal infection with MCMV. Infection-induced ZBTB32 expression was not required for NK cell killing capacity, cytokine production or maturation but it was essential for NK cell clonal expansion. ZBTB32 expression is induced by pro-inflammatory cytokines and promotes NK cell proliferation by suppressing the anti-proliferative factor B lymphocyte-induced maturation protein 1 (BLIMP1).
References
Beaulieu, A. M. et al. The transcription factor Zbtb32 controls the proliferative burst of virus-specific natural killer cells responding to infection. Nature Immunol. http://dx.doi.org/10.1038/ni.2876 (2014)
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Bird, L. Bursting with zinc finger factor. Nat Rev Immunol 14, 355 (2014). https://doi.org/10.1038/nri3697
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DOI: https://doi.org/10.1038/nri3697