Production of stromal cell-derived factor 1 by mesothelial cells and effects of this chemokine on peritoneal B lymphocytes

B1a lymphocytes accumulate and proliferate in the peritoneal cavity. Stroma l cell-derived factor 1 (SDF-1) is a chemotactic and growth promoting facto r for B cell precursors. It is required for fetal liver B cell lymphopoiesi s, which generates mostly B1a lymphocytes. Using immunohistochemistry with an anti-SDF-1 monoclonal antibody, we found that SDF-1 was produced by peri toneal mesothelial cells in adult mice. Peritoneal B1a lymphocytes expresse d a functional SDF-1 receptor, as shown by actin polymerization experiments . In vitro, SDF-1 stimulated migration, proliferation of a minority of peri toneal B1a lymphocytes, and prevented apoptosis in a large fraction of cell s. B1a cells migrating in response to SDF-1 were largely enriched in the CD 5(high)CD43(high)B220(-)CD1d(-) subpopulation. In vivo, neutralization of S DF-1 for 3 weeks significantly decreased the number of peritoneal B1 cells. SDF-1 also acted on peritoneal B2 cells. These findings show that after th e cessation of B cell lymphopoiesis in the liver, around birth, the persist ence of B1a cells remains SDF-1 dependent, and that SDF-1 production by mes othelial cells plays a role in the peritoneal location of B1a cells. Thus, the role of mesothelial cells for B1a cells in adults may be similar to tha t of SDF-1-producing biliary ductal plate cells in the fetus, and to that o f bone marrow stromal cells for B2 cell precursors.