DEFECTS OF B-CELL LYMPHOPOIESIS AND BONE-MARROW MYELOPOIESIS IN MICE LACKING THE CXC CHEMOKINE PBSF SDF-1/

THE chemokines are a large family of small, structurally related cytok ines(1,2). The physiological importance of most members of this family has yet to be elucidated, although some are inducible inflammatory me diators that determine leukocyte chemotaxis(1-5). Pre-B-cell growth-st imulating factor/stromal cell-derived factor-1 (PBSF/SDF-1) is a membe r of the CXC group of chemokines(6,7). PBSF/SDF-1 stimulates prolifera tion of B-cell progenitors in vitro(6) and is constitutively expressed in bone-marrow-derived stromal cells(6,7). Here we investigate the ph ysiological roles of PBSF/SDF-1 by generating mutant mice with a targe ted disruption of the gene encoding PBSF/SDF-1, We found that mite lac king PBSF/SDF-1 died perinatally and that although the numbers of B-ce ll progenitors in mutant embryos were severely reduced in fetal liver and bone marrow, myeloid progenitors were reduced only in the hone mar row but not in the fetal liver, indicating that PBSF/SDF-1 is responsi ble for B-cell lymphopoiesis and bone-marrow myelopoiesis. In addition , the mutants had a cardiac ventricular septal defect, Hence, we have shown that the chemokine PBSF/SDF-1 has several essential functions in development.