IG D-H GENE SEGMENT TRANSCRIPTION AND REARRANGEMENT BEFORE SURFACE EXPRESSION OF THE PAN-B CELL MARKER CD19 IN NORMAL HUMAN BONE-MARROW

The onset of IgH transcription and rearrangement is a defining charact eristic of the progenitor population in which B-lineage commitment occ urs. These features were used to better define the earliest stage of B -cell commitment in humans and to determine if these stages differ as a function of human ontogeny. Fetal and adult bone marrow mononuclear cells were sorted into B-lineage subpopulations on the basis of surfac e expression of the stem cell marker CD34, the pan-B-cell marker CD19, and IgM and analyzed for transcription and rearrangement of the IgH l ocus. The locus was found to be transcriptionally active before surfac e expression of CD19, as indicated by the presence of germline I mu, C mu, and D(H)Q52 transcripts in the CD34(+) CD19(-) subpopulation. Tra nscripts from IgH alleles that had undergone DJC mu rearrangements wer e also detected in the CD34(+) CD19(-) subpopulation, Within this subp opulation, low levels of DXP-containing DJC mu transcripts were detect ed in both fetal and adult cells. Although D(H)Q52 DJC mu transcripts were abundant in fetal CD34(+) CD19(-) cells, they were not detected i n cells of the same phenotype derived from adult bone marrow, In both fetus and adult, V(H)3- and V(H)6-containing VDJC mu transcripts were detected only in the CD19+ subpopulations. These data indicate that tr anscription of D(H)Q52-J(H) and DXP-J(H) rearrangements differs during fetal and adult B lymphopoiesis. Moreover, in both fetus and adult, t ranscription of unrearranged components of the IgH locus and DJ rearra ngements can proceed before the surface expression of CD19. (C) 1997 b y The American Society of Hematology.