LAUSR

Pou2af1 encodes for OCA‐B, a coactivator of OCT‐1/2 transcription factors, which plays a key role in B‐cell maturation. The function of OCA‐B has also been studied in T cells, where T cells from Pou2af1−/− mice have impaired functions, such as cytokine production and T follicular helper (Tfh) differentiation. Arguably, some of these T‐cell phenotypes may result from impaired T–B interactions, secondary to the well‐documented B‐cell defects in Pou2af1−/− mice. Yet, Pou2af1 is actively transcribed in activated T cells, suggesting a T‐cell‐intrinsic role. To isolate the T‐cell‐intrinsic impact of Pou2af1, we generated Pou2af1fl/fl mice with specific genetic disruption of Pou2af1 either in all hematopoietic cells or exclusively in T cells. While we confirm that Pou2af1 is expressed in activated T cells, we surprisingly find that T‐cell cytokine production is not impaired in Pou2af1‐deficient T cells. Moreover, Pou2af1‐sufficient and Pou2af1‐deficient T cells have comparable transcriptome profiles, arguing against a T‐cell‐intrinsic role for Pou2af1. In line with these observations, we demonstrate that Tfh maturation is influenced by T‐cell‐extrinsic deletion of Pou2af1, as observed both in competitive bone marrow chimeras and in Pou2af1fl/fl mice with specific deletion in B cells. Overall, this study provides strong evidence that Pou2af1 does not act as a transcriptional coactivator in T cells, and conclusively demonstrates that loss of OCA‐B in B cells indirectly impacts Tfh differentiation, clarifying the role of OCA‐B in the immune system.