The identities and actions of molecular and cellular mediators of the immune response during chronic viral infections remain poorly understood. In Science, Zuniga and colleagues report that interleukin 6 (IL-6) is essential for viral control during chronic infection with clone 13 lymphocytic choriomeningitis virus (LCMV). IL-6 produced by follicular dendritic cells late in infection is required for the increase in T follicular helper (TFH) cell numbers observed in chronic clone 13 infections and consequently for germinal-center formation and LCMV-specific antibody production. Mechanistically, IL-6 signals in CD4+ T cells in a cell-intrinsic manner to upregulate Bcl-6, a transcription factor required for TFH differentiation. Despite the loss of TFH cells in IL-6-deficient mice, IL-21 remains unchanged, suggesting that there are redundant sources for this cytokine in vivo. IL-6-deficient mice efficiently clear acute (Armstrong clone) LCMV infections.

Science (29 September 2011) doi:10.1126/science.1208421