title: EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues.
abstract: EBV-induced gene 2 (EBI2) was recently shown to direct the delayed movement of activated B cells to interfollicular and outer follicular regions of secondary lymphoid organs and to be required for mounting a normal T-dependent Ab response. In this study, we show that EBI2 promotes an early wave of Ag-activated B cell migration to the outer follicle in mice. Later, when B cells have moved to the T zone in a CCR7-dependent manner, EBI2 helps distribute the cells along the B zone-T zone boundary. Subsequent EBI2-dependent movement to the outer follicle coincides with CCR7 downregulation and is promoted by CD40 engagement. Using a bioassay, we identify a proteinase K-resistant, hydrophobic EBI2 ligand activity in lymphoid and nonlymphoid tissues. Production of EBI2 ligand activity by a cell line is sensitive to statins, suggesting production in a 3-hydroxy-3-methyl-glutaryl-CoA reductase-dependent manner. CD40-activated B cells show sustained EBI2-dependent responsiveness to the bioactivity. These findings establish a role for EBI2 in helping control B cell position at multiple stages during the Ab response and they suggest that EBI2 responds to a broadly distributed lipid ligand.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kelly
authors.forename: João P
authors.initials: JP
authors.lastname: Pereira
authors.forename: Tangsheng
authors.initials: T
authors.lastname: Yi
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000276:immunology* / Q000378:metabolism
chemical_list: C543809:Gpr183 protein, mouse; D008024:Ligands; D043562:Receptors, G-Protein-Coupled