Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B- lineage differentiation capacity

Daniel H. Ryan, Bonnie L. Nuccie, Ion Ritterman, Jane L. Liesveld, Camille N. Abboud, Richard A. Insel

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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-α (IL-7Rα), 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 Igβ, RAG-1, and PAX-5, and were uniformly TdT-positive (TdT+). In contrast, IL-7Rα-/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 Igβ and RAG-1, but not PAX-5, was detected in this fraction, although at lower levels than in the IL-7Rα+ progenitors. In contrast to IL-7Rα, 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-7Rα 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-7Rα 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.

Original languageEnglish
Pages (from-to)929-940
Number of pages12
JournalBlood
Volume89
Issue number3
DOIs
StatePublished - Feb 1 1997

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