Invited Speaker 14th Lorne Infection and Immunity 2024

Divergent cytokine and transcriptional signatures control functional Tfh heterogeneity (#8)

Joanna Groom 1

Flexible immune responses enable clearance and protection against distinct infection types, including viral, bacterial, fungal, and helminth infections. In all these infectious settings, CD4+ T follicular helper (Tfh) cells promote high-affinity class-switched antibodies, long-lived plasma and memory B cells. How Tfh cells tailor B cell responses in a pathogen-specific manner is unclear. Here we identify Tfh transcriptional networks in response to diverse infections. The core Tfh signature, distinct from CD4+ effector and follicular regulatory cells, indicated stem-like potential coordinated by Bcl6. Pathogen-specific signatures highlighted cytokine pathways that establish Tfh heterogeneity and impact B cell output. Cytokine-transcriptional Tfh programing was conserved in human tonsil. This blueprint of Tfh heterogeneity offers new avenues to treat antibody-mediated diseases and inform the development of context-specific vaccines.