Ephrin B1-mediated repulsion and signaling control germinal center T cell territoriality and function

Follicular T helper (T_FH) cells orchestrate the germinal center (GC) reaction locally. Local mechanisms regulating their dynamics and helper functions are not well defined. Here we found that GC-expressed ephrin B1 (EFNB1) repulsively inhibited T cell to B cell adhesion and GC T_FH retention by signaling through T_FH-expressed EPHB6 receptor. At the same time, EFNB1 promoted interleukin-21 production from GC T_FH cells by signaling predominantly through EPHB4. Consequently, EFNB1-null GCs were associated with defective production of plasma cells despite harboring excessive T_FH cells. In a competitive GC reaction, EFNB1-deficient B cells more efficiently interacted with T_FH cells and produced more bone-marrow plasma cells, likely as a result of gaining more contact-dependent help. Our results reveal a contact-dependent repulsive guidance system that controls GC T_FH dynamics and effector functions locally.