A Synchronous IRF4-Dependent Gene Regulatory Network in B and Helper T Cells Orchestrating the Antibody Response

Control of diverse pathogens requires an adaptive antibody response, dependent on cellular division of labor to allocate antigen-dependent B- and CD4⁺ T-cell fates that collaborate to control the quantity and quality of antibody. This is orchestrated by the dynamic action of key transcriptional regulators mediating gene expression programs in response to pathogen-specific environmental inputs. We describe a conserved, likely ancient, gene regulatory network that intriguingly operates contemporaneously in B and CD4⁺ T cells to control their cell fate dynamics and thus, the character of the antibody response. The remarkable output of this network derives from graded expression, designated by antigen receptor signal strength, of a pivotal transcription factor that regulates alternate cell fate choices.