Bcl6 and Blimp-1 Are Reciprocal and Antagonistic Regulators of T Follicular Helper Cell Differentiation

TLDR

B cell–mediated immunity relies on CD4+ T cell help, which is thought to be provided by T follicular helper cells, yet the molecular drivers of T(FH) differentiation remain unclear. Bcl6 is necessary and sufficient for T(FH) differentiation and B cell help, whereas Blimp‑1 antagonizes this process, preventing germinal center formation and antibody responses, underscoring the opposing roles of these transcription factors in T(FH) differentiation.

Abstract

Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits T(FH) differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation.