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. 2022 May;100(5):338-351.
doi: 10.1111/imcb.12543. Epub 2022 Mar 30.

OCA-B does not act as a transcriptional coactivator in T cells

Félix Lombard-Vadnais  1   2 , Julie Lacombe  3 , Geneviève Chabot-Roy  1 , Mathieu Ferron  3   4   5 , Sylvie Lesage  1   6
Affiliations

OCA-B does not act as a transcriptional coactivator in T cells

Félix Lombard-Vadnais et al. Immunol Cell Biol. 2022 May.

Abstract

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.

Keywords: B cells; OCA-B; Pou2af1; T cells; Tfh; germinal centers.

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