Cytokine regulation of early human lymphopoiesis

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

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Abstract

An in vitro culture system in which bone marrow-derived fibroblast-like cells support the growth of TdT+ colonies derived from CD34+/CD10- human bone marrow progenitor cells has recently been described. The regulatory role of cytokines during early B lineage commitment was investigated using this culture system. Expression of IL-7, a cytokine that induces proliferation of B cell precursors, was detectable in the adherent layer by PCR and bioassay. Lymphoid progenitor colonies were inhibited by neutralizing anti-IL-7 Ab, suggesting that IL-7 produced by the adherent layer was required even in the earliest recognizable stages of human B cell lymphopoiesis. IL-1α, IL-4, and TNF-α inhibited lymphoid progenitor colonies in a dose-dependent fashion. Neutralizing Ab to IL-1α, IL-4, or TNF-α did not increase lymphoid progenitor colonies, suggesting that inhibitory concentrations of these cytokines are not constitutively elaborated in the adherent layer. Recombinant Steel factor and IL-6 as well as neutralizing Abs to these cytokines did not significantly affect lymphoid progenitor colonies, arguing against an important role for these cytokines in early human B lymphopoiesis. These results indicate that IL-7 provided by the bone marrow microenvironment is a critical growth factor at the earliest recognizable stages of human lymphopoiesis. IL-1α, IL-4, and TNF-α have been shown to indirectly stimulate release of myeloid growth factors. The inhibition of lymphopoiesis by these cytokines suggests a possible mechanism for the observed reciprocal relationship between lymphoid and myeloid supportive bone marrow microenvironments.

Original languageEnglish
Pages (from-to)5250-5258
Number of pages9
JournalJournal of Immunology
Volume152
Issue number11
StatePublished - Jun 1 1994

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    Ryan, D. H., Nuccie, B. L., Ritterman, I., Liesveld, J. L., & Abboud, C. N. (1994). Cytokine regulation of early human lymphopoiesis. Journal of Immunology, 152(11), 5250-5258.