title: CD9 may contribute to the survival of human germinal center B cells by facilitating the interaction with follicular dendritic cells.
abstract: 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.
authors.affiliation: Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA, USA.
authors.forename: Sun-Ok
authors.initials: SO
authors.lastname: Yoon
authors.affiliation: Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA, USA.
authors.forename: In Yong
authors.initials: IY
authors.lastname: Lee
authors.affiliation: Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA, USA.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Zapata
authors.affiliation: Laboratory of Cellular Immunology, Ochsner Clinic Foundation, New Orleans, LA, USA.
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Choi
keywords: Ag, antigen; Apoptosis; BCR, B cell receptor; CD9; FDC, follicular dendritic cells; Follicular dendritic cells; GC, germinal center; Germinal center B cells; PC, plasma cells; VCAM-1; VLA4