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J Banchereau

Publications and source records attributed to J Banchereau.

At least 235 records · Page 13Linked to original sources
PubMed1992

Interleukin 4 inhibits polyclonal immunoglobulin secretion and cytokine production by peripheral blood mononuclear cells from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is associated with T- and B-cell dysfunction. Immunoglobulin (Ig) production is under the control of T cells and their derived cytokines such as interleukin 2 (IL-2) and IL-4. Herein we studied the regulation of the production of immunoglobulins and cytokines by peripheral blood mononuclear cells from RA patients and controls. In the controls, IL-4 inhibited Ig production in response to Staphylococcus aureus and pokeweed mitogen stimulation. IL-2 induced maximal Ig production in association with Staphylococcus aureus, whereas it inhibited pokeweed mitogen-induced production. In patients, levels of Ig production in response to mitogens and cytokines were reduced, particularly for the response to IL 2. The inhibitory effect of IL-4 on mitogen-induced Ig production was observed in RA patients as in the controls. Spontaneous production of IL-6 was increased in RA patients. These levels were correlated with indicators of active disease such as sedimentation rate and Ritchie index. IL-4 inhibited the production of IL-6, IL-1 beta, and tumor necrosis factor alpha (TNF alpha) by both controls and rheumatoid patients. Thus as first described for the T-cell response, mononuclear cells from RA patients display a reduced response to mitogens and cytokines which induce their B-cell differentiation into Ig-screening cells. However, IL-4 was able to inhibit Ig and cytokine production, properties suggesting a potential antiinflammatory role for this cytokine.

Adolescent↗
PubMed1992

Interleukin 4 inhibits in vitro proliferation of leukemic and normal human B cell precursors.

In the present study, we have investigated the effects of IL-4 on the proliferation and differentiation of leukemic and normal human B cell precursors (BCP). We have demonstrated that IL-4 significantly inhibited spontaneous [3H]thymidine ([3H]-TdR) incorporation by leukemic blasts from some B lineage acute lymphoblastic leukemia (BCP-ALL) patients (8 of 14). Furthermore, IL-4 was found to suppress the spontaneous and factor-dependent (IL-7 and IL-3) proliferation of normal BCP (CD10+ surface [s] IgM- cells) isolated from fetal bone marrow. Maximum growth inhibition of either leukemic or normal BCP was reached at low IL-4 concentrations (10 U/ml), and the effect was specifically neutralized by anti-IL-4 antibody. IL-4 was further found to induce the expression of CD20 antigen on BCP-ALL cells from a number of the cases examined (5 of 8), but in contrast to leukemic cells, IL-4 failed to induce CD20 antigen on normal BCP. Finally, IL-4 was found to induce neither the expression of cytoplasmic mu chain, nor the appearance of sIgM+ cells in cultures of normal or leukemic BCP. Our data indicate that IL-4 has the potential to inhibit cell proliferation in leukemic and normal human B lymphopoiesis but is unable to drive the transition from BCP to mature B cells.

Antigens, CD↗
PubMed1992

Distribution of surface-membrane molecules on bone marrow and cord blood CD34+ hematopoietic cells.

We have investigated the distribution of membrane molecules on CD34+ hematopoietic cells isolated from human bone marrow (BM) and cord blood (CB). A distinct CD10+ population was present in BM, but it was not detected in CB. Most CD34+ CD10+ cells in BM were B-cell precursors (BCP), because they expressed CD19. However, CD40 and CD37 were found on the majority of CD34+ cells from either BM or CB, demonstrating that these antigens are not restricted to B-lineage CD34+ cells. CD40 and CD37 were lost during culture of CD34+ cells in the presence of interleukin 3 (IL-3), indicating transient expression early in myeloid development. CD13 antigen was detected on virtually all CD34+ cells from BM and CB. Accordingly, CD13 was present on CD34+ CD10+ cells, demonstrating that this structure is not restricted to myeloid CD34+ cells. In contrast, myeloid CD33 antigen was not detected on CD34+ CD10+ cells. Expression levels of CD13 and of CD33 were heterogeneous in BM, reflecting diversity within the resident CD34+ population. CD25 and CD71 were found on a proportion of CD34+ cells from either BM or CB and maintained during culture in IL-3, consistent with a distribution on activated cells. Finally, a variety of adhesion receptors were present on CD34+ cells. These included the alpha 4 beta 1 (VLA-4), alpha 5 beta 1 (VLA-5), and alpha L beta 2 (LFA-1) integrins, as well as ICAM-1, LFA-3, H-CAM, and LAM-1. Expression of adhesion receptors was remarkably similar in BM and CB, and it followed an all-or-nothing pattern that failed to delineate CD34+ subsets. Taken together, our data show that although CD34+ cells from BM constitute a more heterogeneous population, resident and circulating CD34+ cells largely display the same cell-surface molecules.

Antigens, CD↗
PubMed1992

Growth and maturation requirements of human B cell precursors.

The present study describes our efforts to induce the proliferation of human B cell precursors (BCP). Committed BCP (CD10+, sIgM-) isolated from fetal bone marrow (18-25 weeks) were induced to proliferate at low levels in the presence of IL7. IL3 potentiated this effect of IL7 on BCP, while IL4 partially inhibited this proliferation. However, neither of these cytokines allowed the emergence of mature B cells. The growth of BCP was strongly potentiated by the presence of an adherent fibroblastic bone marrow stromal layer devoid of cells of hematopoietic origin. Addition of IL7 to such cocultures further increased BCP proliferation. BCP were shown to proliferate as stroma-adherent and non adherent cells. Total cell numbers expanded during 3 weeks, as much as 8 fold in the presence of IL7 when compared with input BCP numbers. Finally, BCP remained sIgM- in stroma dependent cultures, and only a subpopulation of cells became CD20+ in the presence of IL7. Our present study demonstrates the feasibility of human BCP expansion in vitro. However, the signals required for the transition of BCP to mature B cells remain to be determined.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1991

Interleukin-7 induces the proliferation of normal human B-cell precursors.

In the present study, we investigated the effects of human recombinant interleukin-7 (IL-7) on the proliferation of enriched hematopoietic cells isolated from human adult and fetal bone marrow (BM). In cultures of CD34+ cells, IL-7 was found to induce dose-dependent incorporation of 3H-thymidine (3H-TdR), but had no demonstrable effect on the development of myeloid colony-forming cells. Numbers of B-cell precursors (BCP), initially present within CD34+ populations and which included a CD34+CD20+ subset, were significantly increased when CD34+ BM cells were cultured in the presence of IL-7. This effect was most striking on CD20+ BCP, and resulted at least partly from higher numbers of cycling cells as indicated by Hoechst 33342 fluorescence (Calbiochem, Behring Diagnostics, La Jolla, CA). These results indicate that IL-7 promotes the growth of BCP within the CD34+ compartment. In line with the B-lineage affiliation of CD34+ target cells, committed BCP (CD10+ CD19+ surface IgM-) isolated from BM were also found to proliferate in response to IL-7. Interestingly, this effect of IL-7 was strongly potentiated by the addition of IL-3. Taken together, and in accordance with previous observations on murine cells, our data indicate that IL-7 acts as a growth factor during the ontogeny of human B lymphocytes.

Adult↗
PubMed1991

Growing human B lymphocytes in the CD40 system.

One approach to generating human monoclonal antibodies relies on the development of culture techniques allowing the long-term growth of most B lymphocytes, a property of the CD40 system.

Antibodies, Monoclonal↗
PubMed1991

Potentiation of early hematopoiesis by tumor necrosis factor-alpha is followed by inhibition of granulopoietic differentiation and proliferation.

We have previously shown that tumor necrosis factor-alpha (TNF alpha) strongly potentiates interleukin-3 (IL-3)-induced short-term proliferation of human CD34+ hematopoietic progenitor cells (HPC). Using longer term cultures of CD34+ HPC, we demonstrate here that this initial potentiation ceases after 10 to 12 days; whereupon TNF alpha displays inhibitory effects. Thus, TNF alpha was found to inhibit cells of granulocytic affiliation while it potentiates the development of maturing cells of the monocytic lineage both in liquid and semi-solid (day 14 colony-forming unit) cultures. TNF alpha was demonstrated to reversibly block granulocytic differentiation at the level of uncommitted CD13-, CD15- blast cells that accumulate in IL-3 + TNF alpha cultures. Furthermore, growth of committed granulocytes (CD15+) from IL-3 cultures was also inhibited by TNF alpha through an arrest of cell cycle in G0/G1. Finally, the use of neutralizing anti-TNF alpha monoclonal antibody and limiting dilution studies indicate that the inhibitory effects of TNF alpha are direct. Taken together, our data demonstrate that, following a phase of potentiation of proliferation of early HPC, TNF alpha displays direct inhibitory effects due to negative interference with both granulocytic differentiation and proliferation of granulocytic cells.

Antibodies, Monoclonal↗
PubMed1991

Kinetics of interleukin-4 induction and interferon-gamma inhibition of IgE secretion by Epstein-Barr virus-infected human peripheral blood B cells.

Interleukin-4 (IL-4) acts directly on purified human peripheral blood B cells cultured in the presence of Epstein-Barr virus (EBV) to induce IgE secretion and to enhance the secretion of IgG and IgM. Interferon-gamma (IFN-gamma) inhibits IgE secretion in this system, without affecting the secretion of the other Ig isotypes. To identify the time period during which EBV-infected B cells can be induced by IL-4 to secrete IgE, we have studied the effects of delayed addition of IL-4, or the termination of IL-4 stimulation by wash out or by neutralization with anti-IL-4 antibodies, on the induction of an IgE response. To induce a maximal IgE response, IL-4 had to be added to cultures of B cells plus EBV no later than 2 days after the initiation of culture, and had to remain present through the tenth day of culture. These two time points correspond to the initiation of detectable DNA synthesis (Days 3 to 4) and the earliest detectable Ig secretion (Days 10 to 12) by EBV-stimulated B cells. No IgE response was induced if the period during which EBV-stimulated B cells were cultured with IL-4 was less than 4 days, or if IL-4 were added later than the tenth day of culture, regardless of how long the culture was continued beyond that time. In contrast, IL-4 considerably enhanced IgG and IgM secretion and B cell CD23 expression, even if it was added after the tenth day of culture. IFN-gamma strongly inhibited the IgE response of B cells cultured with IL-4 plus EBV if added within 6 days of the initiation of culture, but had little effect on the generation of IgM or IgG responses made by these cells, regardless of the time of addition. Neither IL-4 nor IFN-gamma affected ongoing IgE secretion by an established, IgE-secreting, EBV-transformed cell line. These observations suggest that: (i) IL-4 first becomes able to induce EBV-activated B cells to secrete IgE as these cells begin to synthesize DNA, must stimulate B cells for at least 4 days to induce IgE secretion, and loses its ability to induce IgE secretion as these cells differentiate into Ig-secreting cells; (ii) the ability of IFN-gamma to suppress an IgE response is limited to this same time period; and (iii) IL-4 enhancement of CD23 expression and IgM and IgG secretion are independent of IL-4 induction of an IgE response.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1991

Cross-linking of CD23 antigen by its natural ligand (IgE) or by anti-CD23 antibody prevents B lymphocyte proliferation and differentiation.

The possible role of CD23 in the activation of human B lymphocytes was systematically investigated by examining the effect of: 1) anti-CD23 mAb; 2) IgE or IgE-immune complexes and; 3) native or recombinant soluble CD23 of different m.w., on B cell proliferation. Intact anti-CD23 mAb or its F(ab')2 fragments inhibit the proliferation of tonsillar B lymphocytes costimulated with either Staphylococcus aureus Cowan I (SAC) or anti-IgM and IL-4. The antibody has no effect when IL-2 or LMW-BCGF is used as the second stimulant. The response of IL-4-pretreated B cells (expressing high levels of CD23) to anti-IgM together with IL-2 or B cell-derived B cell growth factor is inhibited by anti-CD23 mAb, indicating that this antibody prevents B cell activation regardless of the B cell activators but provided that the density of CD23 on B cells is sufficient. Anti-CD23 mAb markedly inhibits DNA synthesis only when added during the first 12 h of the culture and has no effect on the ongoing proliferation of CD23-bearing B cell blasts (SAC induced and IL-4 supported or EBV transformed). Monovalent Fab fragments of anti-CD23 mAb are inactive unless they are used in tandem with goat anti-mouse Fab suggesting that the inhibition is due to cross-linking of surface CD23. Most interestingly, polymeric IgE or IgE-immune complexes have the same effect as anti-CD23 and moreover they inhibit IgM production by SAC and IL4-stimulated B cells. The inhibiting effect of IgE or of anti-CD23 mAb is not due to their neutralization of soluble CD23 because these failed to display B cell growth factor activity under various experimental conditions. It is concluded that IgE-immune complexes may regulate activation and differentiation of CD23-bearing surfaceIgM/surfaceIgD precursor B lymphocytes.

Antibodies, Monoclonal↗
PubMed1991

Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen.

Human resting B lymphocytes enter a state of sustained proliferation when incubated with both mouse fibroblastic L cells stably expressing Fc gamma RII/CDw32 and anti-CD40 antibodies. We have explored the effects of 11 recombinant human cytokines (CKs) on induced cell proliferation and immunoglobulin (Ig) production. Interleukin 4 (IL-4) was the only CK able to enhance anti-CD40-induced B cell multiplication as measured by enumeration of viable cells, and interferon gamma (IFN-gamma) further stimulated this induced proliferation. IL-4 enhanced the production of IgM and IgG by B cells and induced them to produce IgE. Combinations of IL-4 and IL-2 resulted in the production of large amounts of IgM and IgA. Interestingly, IFN-gamma did not inhibit the production of IgE by cells stimulated with anti-CD40 and IL-4. None of the tested CK combinations resulted in the production of large quantities of IgG. Therefore, this new culture system represents a unique model to study isotype regulation in highly purified human B lymphocytes, in addition to allowing the generation of long-term factor-dependent human B cell lines.

Antibodies, Monoclonal↗
PubMed1991

Long-term human B cell lines dependent on interleukin-4 and antibody to CD40.

CD40 is a 45- to 50-kilodalton transmembrane glycoprotein expressed on B lymphocytes, epithelial cells, and some carcinoma cell lines. Human resting B lymphocytes entered a state of sustained proliferation when incubated with both the mouse fibroblastic Ltk- cell line that had been transfected with the human Fc receptor (Fc gamma RII/CDw32) and monoclonal antibodies to CD40. In combination with interleukin-4, factor-dependent long-term normal human B cell lines were generated that were consistently negative for Epstein-Barr viral infection. Thus, cross-linking of CD40 is likely to represent an important phenomenon in the clonal expansion of B cells.

Antibodies, Monoclonal↗
PubMed1991

A recombinant extracellular domain of the human interleukin 4 receptor inhibits the biological effects of interleukin 4 on T and B lymphocytes.

Human interleukin 4 (IL4) acts on various hematopoietic cell types through interaction with a specific cell surface receptor (IL4R), whose cDNA has been cloned. We have produced a cDNA encoding a soluble form of the extracellular domain of the human IL 4R (sIL4R) and describe here the capacity of sIL4R to antagonize the in vitro activities of IL4 on normal B and T lymphocytes. sIL4R inhibited IL4-induced proliferation of both phytohemagglutinin-preactivated peripheral blood mononuclear cells (PBMC) and anti-IgM co-stimulated tonsil B cells with similar efficiency. This inhibitory activity was specific since sIL4R did not affect IL2-dependent proliferation of these cells. sIL4R also blocked IL4-dependent induction of the low-affinity receptor for IgE on B cells and inhibited IgE production by IL4-activated PBMC. Thus, in contrast to the IL6R extracellular domain which stimulates IL6 biological activity, the IL4R extracellular domain is a powerful antagonist of its specific ligand.

Antibodies, Anti-Idiotypic↗
PubMed1991

IL-4 and IL-2 upregulate the expression of antigen B7, the B cell counterstructure to T cell CD28: an amplification mechanism for T-B cell interactions.

We recently generated mAb 104 which is specific for the B cell activation antigen Ag B7. With this we studied the regulation of Ag B7 expression on normal tonsillar B lymphocytes as well as the activities of B7+ and B7- activated B cells. SAC and to a lesser extent anti-IgM antibody upregulated Ag B7 and this was further enhanced by IL-2 and most notably IL-4. Ag B7 was expressed on virtually all sIgG+ and sIgA+ B cells and approximately half of the sIgD+ and sIgM+ B cells. SAC-stimulated B7+ B cells proliferated and produced IgM, IgG and IgA in response to IL-2 and IgM and IgG in response to IL-4. SAC-stimulated B7- B cells proliferated and produced only IgM in response to IL-2 and IL-4. Considering that Ag B7 has recently been shown to be the counterstructure of the T cell CD28 and that CD28 triggering strongly enhances cytokine production by T cells, it is likely that the CD28/B7 interaction represents an important amplification phenomenon in T-B cell interaction leading to humoral immune responses. The preferential expression of Ag B7 on IgG and IgA committed cells suggests that CD28/B7 interaction may be more specific to secondary antibody responses provided by memory T and B cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Human interleukin 4.

Human IL-4 is a mature 129 AA glycoprotein, mostly secreted by activated T cells. It is a pleiotropic cytokine which acts on T and B lymphocytes, monocytes, polymorphonuclear cells, fibroblasts and endothelial cells. In addition it acts at various stages of cell differentiation and its effects are also dependent on the cytokine environment. In particular, IL-4 blocks some of the effects of IL-2 whereas interferon gamma blocks some of the effects of IL-4. In vitro and in vivo experiments in mouse and in vitro experiments in man have shown that IL-4 plays a crucial role in the induction of IgE production, whereas interferons counteract this effect. Human IL-4 binds to a high affinity receptor which is composed at least of one 130-kDa glycoprotein of 800 AA, a member of the newly described hematopoietin receptor superfamily. IL-4 may prove useful as an antitumoral and antiinflammatory agent.

Animals↗
PubMed1991

Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents.

Interleukin-4 (IL-4) is one of the products of T-lymphocytes and mast cells, inflammatory cells which accumulate in connective tissues at early stages of fibrosis. We tested the effects of IL-4 on human fibroblasts from normal and scleroderma skin seeded in three dimensional collagen lattices ("dermal equivalents"). IL-4 (10 and 100 U/ml) stimulated collagen synthesis in a dose-dependent manner. No significant alteration of lattice retraction and cell proliferation was observed. At the concentration 100 U/ml, Il-4 was approximately twice more efficient on collagen synthesis than Transforming Growth Factor beta (10 ng/ml). IL-4 secretion in connective tissues might be an important factor for the development of fibrotic processes.

Cells, Cultured↗