The role of recombinant stem cell factor in early B cell development. Synergistic interaction with IL-7.
The cDNA for stem cell factor was recently isolated from Buffalo rat liver cells (BRL-3A) and recombinant rat stem cell factor produced from Escherichia coli (rrSCF164). rrSCF164 synergizes with rhIL-7 to stimulate pre-B clonal growth in agar culture of mouse bone marrow cells, and in this study we have characterized the role of rrSCF164 in B cell development. The combination of rrSCF164 plus rhIL-7 stimulated increased colony numbers compared with the sum of colonies stimulated by rrSCF164 and rhIL-7 alone. Also, increased cell proliferation per colony was stimulated by the combination of rrSCF164 plus rhIL-7 compared with rhIL-7 or rrSCF164 alone. The colonies formed with rrSCF164 plus rhIL-7 and rhIL-7 alone contained exclusively pre-B cells, which expressed B220 Ag and cytoplasmic mu-chain, but were negative for surface Ig expression. Morphological examination of the cells in the colonies showed blast-like characteristics. rrSCF164 alone and in combination with rhIL-7 stimulated generation of B220+ cells in liquid culture of B220- cells, whereas rhIL-7 alone had no stimulatory effect on B220- cells. Both stem cell factor mRNA and bioactivity were detected in a mouse bone marrow-derived stromal cell line, termed OZ-11. We propose that stem cell factor is a stromal-derived factor that synergizes with IL-7 to stimulate the proliferation and differentiation of pro-B cells to pre-B cells, which become responsive to IL-7 alone.
McNiece
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Amgen Inc., Thousand Oaks, CA 91320.
Langley
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KE
Zsebo
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KM
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004357:Drug Synergism; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D015851:Interleukin-7; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019089:Stem Cell Factor