Transcriptional regulation of Tfh dynamics and the formation of immunological synapses

Inside germinal centers (GCs), antigen-specific B cells rely on precise interactions with immune cells and strategic localization between the dark and light zones to clonally expand, undergo affinity maturation, and differentiate into long-lived plasma cells or memory B cells. Follicular helper T (Tfh) cells, the key gatekeepers of GC-dependent humoral immunity, exhibit remarkable dynamic positioning within secondary lymphoid tissues and rely on intercellular interactions with antigen-presenting cells (APCs) during their differentiation and execution of B-cell-facilitating functions within GCs. In this review, we briefly cover the transcriptional regulation of Tfh cell differentiation and function and explore the molecular mechanisms governing Tfh cell motility, their interactions with B cells within GCs, and the impact of their dynamic behavior on humoral responses. This review focuses on T follicular helper (Tfh) cells—cells that are vital to antibody (Ab) production of the immune system. Led by Y.S. Choi, the team outlines how Tfh cells collaborate with B cells in our lymph nodes (small, bean-shaped glands throughout the body) to combat infections. The authors delve into genetic and molecular processes dictating Tfh cells’ actions. Key takeaways highlight the need for precise positioning and timing of Tfh cells with B cells, as well as the critical role of Tfh cell-B cell interaction intensity in B cell affinity maturation. The authors conclude the article by emphasizing the importance of gaining insights into these interactions to develop new therapeutic strategies for autoimmune diseases (conditions where the immune system mistakenly attacks the body), and to enhance vaccine responses. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.