Interleukin 21 Signaling in B Cells Is Required for Efficient Establishment of Murine Gammaherpesvirus Latency

The human gammaherpesviruses take advantage of normal b cell differentiation pathways to establish life-long infection in memory b cells. murine gammaherpesvirus 68 (mhv68) infection of laboratory strains of mice also leads to life-long infection in memory b cells. to gain access to the memory b cell population,mhv68 infected b cells pass through the germinal center reaction during the onset of latency and require signals from t follicular helper (tfh) cells for proliferation. interleukin 21 (il-21),one of the secreted factors produced by tfh cells,plays an important role in both the maintenance of the germinal center response as well as in the generation of long-lived plasma cells. using il-21r deficient mice,we show that il-21 signaling is required for efficient establishment of mhv68 infection. in the absence of il-21 signaling,fewer infected splenocytes are able to gain access to either the germinal center b cell population or the plasma cell population – the latter being a major site of mhv68 reactivation. furthermore,the germinal center b cell population in il-21r-/- mice is skewed towards the non-proliferating centrocyte phenotype,resulting in reduced expansion of infected b cells. additionally,the reduced frequency of infected plasma cells results in a significant reduction in the frequency of splenocytes capable of reactivating virus. this defect in establishment of mhv68 infection is intrinsic to b cells,as mhv68 preferentially establishes infection in il-21r sufficient b cells in mixed bone marrow chimeric mice. taken together,these data indicate that il-21 signaling plays multiple roles during establishment of mhv68 infection,and identify il-21 as a critical tfh cell-derived factor for efficient establishment of gammaherpesvirus b cell latency. © 2015 collins,speck.