EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and non-lymphoid tissues1

• Published in: The Journal of immunology (1950) Vol. 187; no. 6; pp. 3026 - 3032
• Main Authors: Kelly, Lisa M., Pereira, João P., Yi, Tangsheng, Xu, Ying, Cyster, Jason G.
• Format: Journal Article
• Language: English
• Published: 15.08.2011
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1101262

EBI2 was recently shown to direct the delayed movement of activated B cells to inter and outer follicular regions of secondary lymphoid organs and to be required for mounting a normal T-dependent antibody response. Here we show that EBI2 promotes an early wave of antigen-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-T 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 non-lymphoid tissues. Production of EBI2 ligand activity by a cell line is sensitive to statins, suggesting production in an HMG-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 antibody response and they suggest EBI2 responds to a broadly distributed lipid ligand.