Ig DH Gene Segment Transcription and Rearrangement Before Surface Expression of the Pan-B–Cell Marker CD19 in Normal Human Bone Marrow

Abstract

The onset of IgH transcription and rearrangement is a defining characteristic of the progenitor population in which B-lineage commitment occurs. 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 surface expression of the stem cell marker CD34, the pan-B-cell marker CD19, and IgM and analyzed for transcription and rearrangement of the IgH locus. The locus was found to be transcriptionally active before surface expression of CD19, as indicated by the presence of germline I mu, C mu, and D(H)Q52 transcripts in the CD34+ CD19- subpopulation. Transcripts from IgH alleles that had undergone DJC mu rearrangements were also detected in the CD34+ CD19- subpopulation. Within this subpopulation, low levels of DXP-containing DJC mu transcripts were detected in both fetal and adult cells. Although D(H)Q52 DJC mu transcripts were abundant in fetal CD34+ CD19- cells, they were not detected in 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 transcription of D(H)Q52-J(H) and DXP-J(H) rearrangements differs during fetal and adult B lymphopoiesis. Moreover, in both fetus and adult, transcription of unrearranged components of the IgH locus and DJ rearrangements can proceed before the surface expression of CD19.