Modeling the Synergetic Dynamics of B cells and TFH cells in Germinal Center Reactions

B cells producing high-affinity antibodies arise through affinity maturation within germinal centers (GCs), where selection is driven by T follicular helper (T _FH ) cells. Recent studies have shown that, like GC B cells, T _FH cells also undergo antigen-dependent selection, with competition among T _FH clones dictated by their ability to recognize and stimulate B cells. This sensitivity-dependent selection process leads to dynamic remodeling of the T _FH repertoire over time. Despite the essential role of T _FH cells in B cell selection, the functional consequences of the time evolution of the T _FH cell population remains poorly understood. To address this gap, we developed a population dynamics model that explicitly incorporates key T _FH cell properties and dynamics. Our analysis predicts that dynamic feedback between B and T _FH cell populations provides robust homeostatic regulation of their numbers in the GC, yielding a stable lymphocyte ratio that we verify experimentally. Moreover, our model predicts that T _FH clone sensitivity dictates distinct evolutionary strategies during affinity maturation, with low-sensitivity T _FH cells accelerating affinity gain at the expense of B cell diversity, while high-sensitivity T _FH cells slow affinity maturation but preserve a broader B cell repertoire. These findings highlight the importance of co-regulation between T _FH and B cells and suggest that reciprocal stimulation allows the immune system to tune the tradeoff between the speed of affinity gain and the breadth of B cell diversity—a principle that may extend to other adaptive systems.