IFNg-producing Tfh cells control the differentiation of lung resident memory B cells

T follicular helper (Tfh) cells are a specific subset of CD4 T cells that localize in the B cell follicle and are essential for the Germinal Center (GC) response. Under polarizing environments, Tfh cells produce IFN-g. Beyond promoting class switching, the role played by IFN-g-producing Tfh cells remains largely unexplored. Using an influenza infection model, we show here that interactions with IFN-? producing Tfh cells during the peak of the response skew the GC B cell response towards the memory differentiation pathway. Consequently, lung-memory B cells fail to differentiate without IFN-? producing Tfh cells. Collectively, our results support a model in which temporary changes in cytokine production by Tfh cells dynamically control the outcome of the GC response. Overall design: RNAseq was performed for the following (in triplicate for each sample type): 1. C57BL/6 mice were irradiated and reconstituted with a 50:50 mix of bone marrow from CD45.1+ B6 (WT) and CD45.2+ IfngR1-/- donors. Eight weeks later, reconstituted mice were infected with PR8 influenza virus, and WT and IfngR1-/- GC B cells were sorted from the lung-draining mediastinal lymph node on day 12 after infection; 2. C57BL/6 mice were infected with PR8, and GC B cells from the lung-draining mediastinal lymph node and CXCR3+ memory B cells from the lungs were sorted on day 30; and 3. C57BL/6 mice were infected with PR8 and CXCR3+, and CXCR3- GC B cells were sorted from the lung-draining mediastinal lymph node on day 12.