OCA-B/Pou2af1 is sufficient to promote CD4⁺ T cell memory and prospectively identifies memory precursors.

Abstract

The molecular mechanisms leading to the establishment of immunological memory are inadequately understood, limiting the development of effective vaccines and durable antitumor immune therapies. Here, we show that ectopic OCA-B expression is sufficient to improve antiviral memory recall responses, while having minimal effects on primary effector responses. At peak viral response, short-lived effector T cell populations are expanded but show increased <i>Gadd45b</i> and <i>Socs2</i> expression, while memory precursor effector cells show increased expression of <i>Bcl2</i>, <i>Il7r,</i> and <i>Tcf7</i> on a per-cell basis. Using an OCA-B mCherry reporter mouse line, we observe high OCA-B expression in CD4⁺ central memory T cells. We show that early in viral infection, endogenously elevated OCA-B expression prospectively identifies memory precursor cells with increased survival capability and memory recall potential. Cumulatively, the results demonstrate that OCA-B is both necessary and sufficient to promote CD4 T cell memory in vivo and can be used to prospectively identify memory precursor cells.