Expression of interleukin-4 receptors on early human B-lineage cells

Law, CL; Armitage, R; Villablanca, JG; LeBien, Tucker W.

doi:10.1182/blood.v78.3.703.bloodjournal783703

Cited by 4 publications

(4 citation statements)

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“…The high SSC population expressed high levels of cell surface CD23, a broadly distributed 45-kD glycoprotein (33). CD23 has been described to represent a stagespecific marker on slgM + B cells before isotype switching in B cell ontogeny (34,35). The present data, however, demonstrate that CD23 is inducible before acquisition of slgM.…”

Section: Discussioncontrasting

confidence: 54%

“…In parallel to our results on BCP, it is of interest that mature B cells have recently been reported to acquire CD23 upon culture in the CD40 system (36). Unlike its effect on mature B cells (37), IL-4 does not appear able to promote CD23 expression on BCP (35) (our unpublished data). Thus, CD40-mediated induction of CD23 on BCP could be independent of IL-4.…”

Section: Discussionmentioning

confidence: 80%

See 1 more Smart Citation

Human B cell precursors proliferate and express CD23 after CD40 ligation.

Saeland¹,

Duvert²,

Moreau³

et al. 1993

The Journal of Experimental Medicine

110

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SllmmaryThe CD40 surface membrane molecule plays an important role in the activation of mature human B cells, but its role in earlier stages orB lineage development is unknown. Here, we have investigated the effects of triggering the CD40 antigen on B cell precursors (BCP) by crosslinking with anti-CD40 antibody presented by Fc'/-receptor type II-transfected murine Ltk-cells (CD40 system). CD10 + surface immunoglobulin negative (slg-) BCP, freshly isolated from fetal bone marrow or precultured on stromal cells, proliferated in the CD40 system. This effect required the presence of IL-3, which acted as a specific cosignal among a panel of cytokines examined. The association of IL-10 and IL-7 potentiated the observed IL-3 and CD40-dependent BCP proliferation, demonstrating that IL-10 can act on early B lineage cells. CD40-dependent activation of fetal BCP did not favor maturation to slg + B cells, but resulted in the induction of high levels of surface membrane CD23. The emerging CD23 + BCP lacked slg and CD10, and represented an important proportion of the cycling cells in the CD40-dependent cultures. Taken together, our data demonstrate that stimulation of the CD40 antigen induces expression of the CD23 gene, and regulates cell proliferation during normal human B cell ontogeny.T he life history orB lymphocytes can be divided into two major steps. First, an antigen-independent process (B lymphopoiesis) permits constant generation of new immunocompetent surface (s)llgM + slgD + mature B cells in the bone marrow (for reviews see references 1 and 2). Then, mature B cells can be driven by antigens to proliferate and differentiate in secondary lymphoid organs (immunopoiesis) (for a review see reference 3). Both soluble cytokines and cell membrane-associated molecules regulate the various steps of B lymphocyte development. In this context, the CD40 B cell surface membrane molecule has recently been identified as playing a fundamental role in the process of immunopoiesis. Human CD40 is a 50-kD glycosylated phosphoprotein (4), that belongs to a new superfamily of receptors that includes the receptors for nerve growth factor and TNF (5, 6).Anti-CD40 antibody presented by Fc',/receptor type II (Fc'yRII) (CDw32)-transfected murine fibroblastic Ltkcells (CD40 system) induces strong and long-lasting B cell expansion in the presence of IL-4 (7, 8). The proliferation of anti-CD40-activated mature B cells is also enhanced by IL-10 (9). More strikingly, IL-10 allows CD40-activated B cells to produce large quantities of IgM, IgG, and IgA after their differentiation into plasma cells. Culturing CD40-activated naive slgD + slgM + B cells in the presence of IL-4 or IL-10 and TGF-~ induces the production of IgE or IgA, respectively, as a consequence of isotype switching (10-14).Recent studies have indicated that CD40 crosslinking represents the first step of the interaction between T and B cells. A ligand to CD40 has recently been identified and expressed from activated T cells, and CD40-Ig fusion proteins inhibit T cell-dependent B ce...

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 80%

Human B cell precursors proliferate and express CD23 after CD40 ligation.

Saeland¹,

Duvert²,

Moreau³

et al. 1993

The Journal of Experimental Medicine

110

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“…We examined IL-4 because it is the most effective cytokine for culturing mature B cells in the 'CD40 system'. Besides, IL-4 receptors are expressed on leukaemic B-cell precursors (Law et al, 1991), although IL-4 was also reported to be toxic for leukaemic B-cell precursors (Okabe et al, 1991;Manabe et al, 1994). Indeed, we found a clear suppressive effect of IL-4 on the growth of ALL cells.…”

Section: Time Curvesmentioning

confidence: 50%

Proliferation of precursor B‐lineage acute lymphoblastic leukaemia by activating the CD40 antigen

Planken¹,

Dijkstra²,

Bâkkus³

et al. 1996

Br J Haematol

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No reliable culture system exists for B-lineage acute lymphoblastic leukaemia (ALL). Recently we found that many different mature B-cell malignancies proliferate upon stimulation via the CD40 antigen, and this led us to investigate whether a similar CD40 activation on ALL cells could also induce proliferation. First, we measured CD40 expression in 21 ALL cases; all were CD40+, although mostly weak. Next, we triggered the CD40 antigen by anti-CD40 antibodies and by a CD40 ligand-expressing cell line. In addition, we measured the influence of IL-3, IL-4 and IL-7 with and without these stimuli. In 8/10 cases proliferation, measured by 3H-thymidine incorporation, could be induced after CD40 crosslinking, especially in the presence of IL-3. Stimulation via the CD40 ligand was more successful than using crosslinked anti-CD40 antibodies. IL-4 inhibited the spontaneous proliferation found in three cases, but stimulated proliferation after CD40 crosslinking. IL-7 did not contribute to proliferation. Morphology, immunophenotyping and surface marker analysis, combined with DNA flow cytometry confirmed that the proliferation found could be ascribed to the ALL cells. In conclusion, B-lineage ALL cases are CD40+, and many can be cultured using CD40 stimulation and IL-3.

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“…Indeed CLL is due to the malignant proliferation of B cells that are arrested ("frozen") at a discrete stage of their maturation. Finally, it is of note that malignant pre-B cells, from patients with acute lymphoblastic leukemia, may be induced to express CD23 following stimulation with IL-4 (Law et al, 1991).…”

Section: Cellular Distributionmentioning

confidence: 99%