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Ephrin-B1-Mediated Regulation of Germinal Center T-Cell Territoriality and Function
Lü Peiwen, Shi Changming, Qi Hai*
Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
Abstract: Follicular T-helper (TFH) cells play a crucial role in orchestrating the germinal center (GC) response. It is not clear whether and how their recruitment and helper functions are regulated locally. We have found GC-expressed Ephrin-B1 (EFNB1) serves as a contact-dependent， repulsive guidance cue that signals through TFH-expressed EphB6 receptor to inhibit T-B adhesion and GC retention of TFH cells. EFNB1 also signals through EphB4 and EphB6 to promote interleukin-21 (IL-21) production. As a result， EFNB1-null GCs are defective in producing plasma cells despite harboring excessive TFH cells， whereas in a competitive GC reaction EFNB1- deficient B cells produce more bone-marrow plasma cells as a result of gaining more contact-dependent T cell help. These results reveal a new layer of self-organizing regulatory mechanisms for the GC reaction locally.
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