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Expression of interleukin-7 receptor by lineage-negative human bone marrow
progenitors with enhanced lymphoid proliferative potential and B- lineage
differentiation capacity
DH Ryan, BL Nuccie, I Ritterman, JL Liesveld, CN Abboud and RA Insel
Department of Pathology and Laboratory Medicine, University of Rochester
Medical Center, NY, USA.
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.
Volume 89,
Issue 3,
pp. 929-940,
02/01/1997
Copyright © 1997 by The American Society of Hematology
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