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

Abstract

Summary: Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH 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 TFH 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 TFH cells. Sema4C on TFH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases TFH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH 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 TFH recruitment and function and optimize antibody responses. : Yan et al. identify Plexin B2 and Semaphorin 4C as an antigen-independent, contact-dependent guidance system that promotes GC recruitment of follicular T helper cells, a process crucial for productive antibody responses. When PlxnB2 or Sema4C is absent, follicular T helper cells are mislocalized and plasma cell generation and affinity maturation are defective. Keywords: humoral immunity, germinal center, follicular T-helper cells, Plexin B2, Semaphorin 4C, Semaphorin 4D, cell migration, cell adhesion, intravital imaging, plasma cells