Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

Follicular T helper (T-FH) cells orchestrate the germinal center (GC) response locally. T-FH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for T-FH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on T-FH cells. Sema4C on T-FH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases T-FH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from T-FH cells causes T-FH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC T-FH recruitment and function and optimize antibody responses.