Growth inhibitory and agonistic signals of interleukin-7 (IL-7) can be mediated through the CDw127 IL-7 receptor

Abstract

The present study was aimed at identifying surface-membrane molecules involved in the regulation of human B-cell ontogeny. For this purpose, murine monoclonal antibodies (MoAbs) were generated against Pre-Alp, a pre-B acute lymphoblastic leukemia (ALL) cell line, and MoAb R34.34 was selected for further characterization. R34.34 recognized a molecule expressed on normal B-cell precursors (BCP) but not on mature B cells. The antibody also reacted with T lymphocytes, a subpopulation of monocytes from peripheral blood, and a subset of CD34+ cells. Immunoprecipitation analysis indicated that R34.34 recognizes an 80-kD molecular weight antigen. Antibody R34.34 was further found to be directed against an epitope interfering with binding of interleukin-7 (IL-7) to Pre-Alp cells. Expression cloning from a Pre-Alp cDNA library showed that R34.34 antigen is CDw127, the 75- to 80-kD IL-7 receptor. Proliferation of the B-lineage ALL cell lines Reh and Mieliki was inhibited by IL-7, and this effect was specifically reverted by MoAb R34.34. In addition, antibody R34.34 specifically inhibited IL-7- dependent proliferation of normal BCP, Pre-Alp cells, and peripheral T cells. These results imply that both inhibitory and proliferative effects of IL-7 can be mediated through the same receptor on various lineages. R34.34 antibody should be important for the analysis of signal transduction through CDw127.

Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.

“…In view of this R A G -1 and R A G -2 downmodulation, the progression of heavy chain gene rearrangement to generate p~+ pre-B cells would not be anticipated, and the lack of an IL-7 effect on cytoplasmic p~ chain expression was confirmed by immunofluorescence analysis after permeabilization of the isolated pro-B cells. The addition of an antagonistic a n t i -I L -7 R antibody (60) to the IL-7-treated cultures blocked the downregulation of R A G and T d T m R N A levels, thus confirming the involvement of the IL-7 R in mediating the IL-7 effects (Fig. 3 A).…”

“…This interpretation is reinforced by the specificity of the IL-7 effect in that the expression of genes encoding the Ig receptor components IgH, IgL, Ig{x, and Ig[3 was totally unaffected by IL-7 treatment. Moreover, the downregulatory effects of the IL-7 treatment on the TdT, RAG-l, and RAG-2 genes were abrogated by an anti-IL-7R antibody with proven antagonist characteristics (60).…”

Profiling of genes expressed in human monocytes and monocyte‐derived dendritic cells using cDNA expression array

“…Our data are in agreement with those of recent studies, in terms of constitutive expression of IL‐2 and IL‐7 receptors, both on the cell surface and intracellularly in monocytes. Activated IL‐2 and IL‐7 receptors can induce intracellular signalling for cell proliferation (Pandrau‐Garcia et al , 1994; Hodge et al , 2000). These results again confirm that the cell cycle in monocytes is much more active and, therefore, monocytes can differentiate into DCs.…”

Multiple γc‐receptor expression in adult T‐cell leukemia

“…IL‐7 stimulated DNA synthesis in ALL cells of B‐cell precursor origin as well as immature T‐cell origin (30), and a pre‐B ALL cell line that proliferates in response to IL‐7 was established (31). A monoclonal antibody against IL‐7Rα (CD127), R34.34, was generated (32), and the expression of IL‐7R was assessed by flow cytometry in ALL (33). As expected, the majority of T‐ALL cases and approximately half of B‐ALL cases were CD127‐positive.…”