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-γ 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-γ 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. 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.