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PU. 1 is an ETS family transcription factor that is important for the development of multiple hematopoietic cell lineages. Previous work demonstrated a critical role for PU. 1 in promoting Th9 development and in limiting Th2 cytokine production. Whether PU. 1 has functions in other Th lineages is not clear. In this study, we examined the effects of ectopic expression of PU. 1 in CD4+ T cells and observed decreased expression of genes involved with the function of T follicular helper (Tfh) cells, including Il21 and Tnfsf5 (encoding CD40L). T cells from conditional mutant mice that lack expression of PU. 1 in T cells (Sfpi1 lck−/−) demonstrated increased production of CD40L and IL-21 in vitro. Following adjuvant-dependent or adjuvant-independent immunization, we observed that Sfpi1 lck−/− mice had increased numbers of Tfh cells, increased germinal center B cells (GCB cells), and increased Ab production in vivo. This …