B-LYMPHOCYTE CHEMOTAXIS REGULATED IN ASSOCIATION WITH MICROANATOMIC LOCALIZATION, DIFFERENTIATION STATE, AND B-CELL RECEPTOR ENGAGEMENT

Migration of mature B lymphocytes within secondary lymphoid organs and recirculation between these sites are thought to allow B cells to obt ain T cell help, to undergo somatic hypermutation, to differentiate in to effector cells, and to home to sites of antibody production. The me chanisms that direct migration of B lymphocytes are unknown, but there is evidence that G protein-coupled receptors, and possibly chemokine receptors, may be involved. Stromal cell-derived factor (SDF)-1 alpha is a CXC chemokine previously characterized as an efficacious chemoatt ractant for T lymphocytes and monocytes in peripheral blood. Here we s how with purified tonsillar B cells that SDF-1 alpha also attracts nai ve and memory, but not germinal center (GC) B lymphocytes. Furthermore , GC B cells could be converted to respond to SDF-1 alpha by in vitro differentiation into memory B lymphocytes. Conversely, the migratory r esponse in naive and memory B cells was significantly reduced after B cell receptor engagement and CD40 signaling. The receptor for SDF-1, C XC chemokine receptor 4 (CXCR4), was found to be expressed on responsi ve as well as unresponsive B cell subsets, but was more rapidly downre gulated on responsive cells by ligand. Finally, messenger RNA for SDF- 1 was detected by in situ hybridization in a layer of cells surroundin g the GC. These findings show that responsiveness to the chemoattracta nt SDF-1 alpha is regulated during B lymphocyte activation, and correl ates with positioning of B lymphocytes within a secondary lymphoid org an.