IMMUNOLOGY2024™ Conference Recordings-Control of extrafollicular vs. germinal center responses in immunity and autoimmunity

Control of extrafollicular vs. germinal center responses in immunity and autoimmunity

Video Transcription

Video Summary

The speaker discussed how immune responses split between extrafollicular (EF) and germinal center (GC) pathways, especially during infection and autoimmunity. He emphasized that GC responses mainly optimize clonal selection and long-term protection, while EF responses provide rapid, early antibody and cytokine production. Using Salmonella infection as a model, the team found that inflammation strongly suppresses GC formation and drives EF plasmablast responses.<br /><br />A key discovery was that IL-12 is a major switch controlling this balance. IL-12 blocks T follicular helper differentiation and GC formation, while promoting plasmablast accumulation. Importantly, IL-12 acts on both B cells and T cells. B cells respond to IL-12 by producing interferon gamma, which creates a positive feedback loop with IL-12 signaling. This loop sustains gene expression programs that favor proliferation, plasmablast differentiation, and Th1-like responses, while suppressing GC development.<br /><br />The speaker concluded that inflammation, especially IL-12-driven signaling, can tilt immune responses toward EF effector function rather than GC formation. This framework may help explain infection outcomes, autoimmune disease, and potentially guide therapies targeting specific immune cell pathways.

Keywords

extrafollicular response

germinal center

IL-12

plasmablast differentiation

T follicular helper

Salmonella infection

interferon gamma