Loss of c-kit accompanies B-lineage commitment and acquisition of CD45R bymost murine B-lymphocyte precursors

Using surface markers, we identified two bone marrow (BM) subsets enriched for TdT(+) cells on the brink of CD45R acquisition, These two populations, Lin(-)c-kit(Lo) and Lin(-)c-kit(-), consisting of 35.4% and 7.4%, respectiv ely, TdT(+) cells, generated B-lineage cells in overnight cultures. Approxi mately half of the c-kit(Lo) B-lineage precursors were bipotential, yieldin g myeloid and lymphoid progeny, whereas most that were c-kit(-) gave rise o nly to lymphocytes. Analysis of B-lineage progression during a finite cultu re period showed that the most mature precursors were concentrated in the L in-c-kit- population. Moreover, a majority of the earliest CD45R(+) pro-B c ells in BM, identified as CD45R(+) CD43(+) BP-1(-) CD25(-) natural killer ( NK)1.1(-) sIgM-, were also c-kit-, These c-kit- cells, like their c-kit(Lo) counterparts, expressed TdT, proliferated in response to interleukin (IL)- 7, and generated slgM(+) cells. These data suggest that TdT expression is i nitiated as c-kit downregulation begins in Lin(-) cells, with progressive l oss of c-kit during B-Lineage differentiation. CD45R expression is initiate d during the transition from C-kit(Lo) to c-kit- with many cells losing c-k it before acquiring CD45R. The ability to isolate highly enriched populatio ns of viable CD45R(-) precursors will be instrumental in characterizing the earliest B-lineage cells. (C) 1999 by The American Society of Hematology.