Immunobiologic differences between normal and leukemic human B-cell precursors

Abstract

The early stages of normal human B-cell differentiation were studied by flow cytometry and cell sorting based on expression of CD10 (CALLA) and CD19 antigens in fetal liver. Both CD10+ CD19+ and CD10+ CD19- precursor populations proliferated in vitro to form B-cell precursor colonies under stimulation from low molecular weight B-cell growth factor (L-BCGF) or recombinant interleukin 3 but did not respond to high molecular weight B-cell growth factor (H-BCGF). The colonies derived from the CD10+ CD19- fraction showed induction of CD19 expression in 10-50% of growing cells, suggesting that CD10 expression precedes CD19 expression in B-cell ontogeny. This hypothesis was corroborated by less-differentiated marker profiles of the progeny of CD10+ CD19- B-cell precursors as compared to CD10+ CD19+ B-cell precursors in BCGF-stimulated cultures and by higher percentages of CD10+CD19- versus CD10-CD19+ B-cell precursors. CD19 crosslinking on normal fetal liver or bone marrow B-cell precursors was associated with an increase in cytoplasmic calcium concentration, but was inhibitory for colony formation. Leukemic B-cell precursors from acute lymphoblastic leukemias (ALLs) differed from normal B-cell precursors in their in vitro proliferative responses, since (i) they responded not only to L-BCGF and rIL-3 but also to H-BCGF and (ii) their proliferation was stimulated rather than inhibited by CD19 crosslinking. A clonogenic leukemic counterpart for the CD10+CD19- normal B-cell precursor population does not exist among malignant cells from B-cell precursor ALL patients, suggesting that the CD19 receptor may be involved in leukemogenesis of human B-cell precursor ALL.