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

Guiding immune cells to the center Germinal centers (GCs) are the site of antibody affinity maturation. The GC response fundamentally depends on contact-dependent signal exchange between antigen-specific T and B lymphocytes. Lu et al. uncovered a repulsive guidance system that inhibits GC recruitment and retention of T follicular helper (T FH ) cells while simultaneously promoting their helper activities locally (see the Perspective by Moschovakis and Forster). This system comprises the GC-specific transmembrane ephrin B1 (EFNB1) molecule and two EFNB1 receptors—EPHB4 and EPHB6—expressed by activated T cells, including T FH cells. In the absence of EFNB1 on GC B cells or when EPHB6 was suppressed on T cells, inappropriately large numbers of T cells were recruited to and retained in the GC as a result of relaxed repulsion of T FH cells. Science , this issue p. eaai9264 ; see also p. 703