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

摘要

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.