Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B-lineage differentiation capacity.
Relatively little is known about the relationship of lymphoid-associated gene expression to the proliferation and differentiation potential of early human bone marrow lymphoid progenitors. Surface expression of interleukin-7 (IL-7) receptor-alpha (IL-7R alpha), a component of the high-affinity receptor for the lymphoid precursor growth factor IL-7, defined a CD34+ progenitor subset lacking the CD19+ pro-B phenotype but demonstrating markedly enhanced lymphoid clonogenic capacity and the ability to differentiate into pro-B cells in short-term culture. These progenitors expressed mRNA for the lymphoid-associated genes Ig beta, RAG-1, and PAX-5, and were uniformly TdT-positive (TdT+). In contrast, IL-7R alpha-/CD19-/ CD34+ progenitors had a 50-fold reduced lymphoid clonogenic capacity and did not differentiate into pro-B cells in short-term culture. Expression of TdT and the lymphoid-associated genes Ig beta and RAG-1, but not PAX-5, was detected in this fraction, although at lower levels than in the IL-7R alpha+ progenitors. In contrast to IL-7R alpha, loss of the stem cell factor receptor c-kit was associated with enhanced lymphoid clonogenic potential and increased B-lineage differentiation potential. These results indicate that IL-7R alpha expression defines entry into a developmental stage characterized by upregulation of multiple lymphoid-associated genes and enhanced fitness for B-lymphoid differentiation. The onset of IL-7R alpha and PAX-5 expression immediately before acquisition of CD19 is consistent with evidence suggesting upregulation of CD19 through pathways involving PAX-5 and IL-7.
Ryan
D H
DH
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY, USA.
Nuccie
B L
BL
Ritterman
I
I
Liesveld
J L
JL
Abboud
C N
CN
Insel
R A
RA
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D018941:Antigens, CD19 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics; D002999:Clone Cells; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D020395:Receptors, Interleukin-7
D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D015851:Interleukin-7; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D019009:Proto-Oncogene Proteins c-kit; D004253:DNA Nucleotidylexotransferase; D017493:Leukocyte Common Antigens