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The germinal center (GC) is a dynamic microenvironment where antigen (Ag)‐activated B cells rapidly expand and differentiate, generating plasma cells (PC) that produce high‐affinity antibodies. Precise regulation of survival and proliferation of Ag‐activated B cells within the GC is crucial for humoral immune responses. The follicular dendritic cells (FDC) are the specialized stromal cells in the GC that prevent apoptosis of GC‐B cells. Recently, we reported that human GC‐B cells consist of CD9+ and CD9− populations and that it is the CD9+ cells that are committed to the PC lineage. In this study, we investigated the functional role of CD9 on GC‐B cells. Tonsillar tissue section staining revealed that  in vivo  CD9+ GC‐B cells localized in the light zone FDC area. Consistent this,  in vitro  CD9+ GC‐B cells survived better than CD9− GC‐B cells in the presence of HK cells, an FDC line, in a cell–cell contact‐dependent manner. The frozen tonsillar tissue section binding assay showed that CD9+ GC‐B cells bound to the GC area of tonsillar tissues significantly more than the CD9− GC‐B cells did and that the binding was significantly inhibited by neutralizing anti‐integrin β1 antibody. Furthermore, CD9+ cells bound to soluble VCAM‐1 more than CD9− cells did, resulting in activation and stabilization of the active epitope of integrin β1. All together, our data suggest that CD9 on GC‐B cells contributes to survival by strengthening their binding to FDC through the VLA4/VCAM‐1 axis.

CD9 may contribute to the survival of human germinal center B cells by facilitating the interaction with follicular dendritic cells