EARLY-ONSET OF IMMUNOGLOBULIN HEAVY-CHAIN GENE REARRANGEMENTS IN NORMAL HUMAN BONE-MARROW CD34(+) CELLS

To characterize early B-cell precursors in humans, we correlated immun oglobulin heavy chain (IgH) gene rearrangement status with the CD34, C D19, and CD10 cell surface markers. Highly purified adult bone marrow (BM) cell fractions were obtained by two successive rounds of flow cyt ometric cell sorting, and IgH rearrangements were analyzed by polymera se chain reaction (PCR) amplification. Complete VDJ(H) rearrangements were observed in the CD34(+) CD19(+) fraction, but not in the more imm ature CD34(+) CD19(-) fraction. About one quarter of these rearrangeme nts had an open reading frame, thus potentially permitting the synthes is of a mu chain. Partial DJ(H) rearrangements were detected in both C D34(+) CD19(+) and CD34(+) CD19(-) subsets, although they were less ab undant in the latter. When triple labeling was used to better characte rize the CD34(+) CD19(-) population, DJ(H) rearrangements were found t o be present in the CD34(+) CD10(+) CD19(-) fraction, but not in the m ore primitive CD34(+) CD10(-) CD19(-). These results indicate that IgH gene rearrangements occur in CD34(+) PM cells and that they initiate in immature progenitors expressing the CD10. but not yet the CD19 surf ace antigen. Finally, the presence of IgH gene rearrangements in CD34( +) PM cells provides a useful marker of clonality to evaluate the poss ible involvement of these cells in various B-cell lymphoid malignancie s. (C) 1997 by The American Society of Hematology.