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Biomedical subjects

I Durand

Publications and source records attributed to I Durand.

At least 55 records · Page 3Linked to original sources
PubMed1995

Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid up-regulation of B7-1 and B7-2.

Human memory B cells that carry mutated IgV region genes were isolated from tonsils by negative selection of IgD+ naive B cells and CD38+ germinal center B cells and plasma cells. They were mainly found within the intraepithelial areas, but not in the B cell follicles of human tonsils. Memory B cells but not naive B cells have the capacity to present antigen directly to T cells, owing to the constitutive expression of the accessory molecules B7-1/CD80 and B7-2/CD86. Signals through antigen receptors and CD40 antigen result in these two molecules being further up-regulated more rapidly and strongly on memory B cells than on naive B cells. The unique anatomical localization of memory B cells beneath the surface of mucosa, together with their strong APC capacity, may explain the well-known prompt and robust secondary antibody responses.

Antigen-Presenting Cells↗
PubMed1995

T cell-induced B cell blasts differentiate into plasma cells when cultured on bone marrow stroma with IL-3 and IL-10.

B lymphocytes activated by T cells in secondary lymphoid organs mature into plasma cells after migration into the medullary cords of these organs, mucosal lamina propria or bone marrow. To analyze each step leading to plasma cell generation, we set up a two-step culture system of purified tonsillar B cells. In a primary stage, B cell blasts were generated by co-culturing B cells with an irradiated T cell clone activated with immobilized anti-CD3. In a secondary step, culturing these blasts on bone marrow stromal cells (BMSC) induced them to secrete large amounts of IgG, as well as some IgM and IgA. Other fibroblast-like cell lines were less efficient at sustaining the differentiation of blasts into Ig-secreting cells, suggesting that these are specific properties of BMSC. Addition of IL-3 and IL-10 further stimulated IgG secretion by B cell blasts cultured on BMSC, mostly the IgG1 subclass. These two cytokines probably acted through different pathways, as (i) the effect of IL-3 but not IL-10 was dependent upon prolonged T cell pre-activation and (ii) their combined stimulatory effect was additive. B cell blasts cultured on BMSC with a combination of IL-3 and IL-10 differentiated into non-proliferating plasma cells as determined by poor thymidine incorporation, typical cellular morphology, intense expression of intracytoplasmic Igs, very high levels of surface CD38 and lack of surface CD20.

Adult↗
PubMed1995

The ability of synoviocytes to support terminal differentiation of activated B cells may explain plasma cell accumulation in rheumatoid synovium.

To understand the accumulation of plasma cells within RA synovium, the ability of rheumatoid synoviocytes to support the differentiation of B cells into plasma cells was explored. Tonsillar B lymphocytes cultured over confluent monolayers of synoviocytes, secreted threefold more Igs (mainly IgM) than B cells cultured directly on plastic well. More importantly, synoviocytes enhanced by 14-fold the production of Igs (mainly IgG) by B cells costimulated with Staphylococcus aureus Cowan (SAC) particles. IL-10 and, in a lower extent, IL-2 increased Ig secretion in cocultures, and their combination was synergistic. In the presence of SAC, IL-2, and IL-10, synoviocytes increased by 13-884-fold the production of IgG, which reached 0.19 ng/cell per day. RA as well as normal synoviocytes were more potent than other adherent cell lines to support terminal B cell differentiation. Synoviocyte activity involved both a support of B cell survival, and an induction of the terminal differentiation of B cells into mature plasma cells with typical morphology, high levels of intracytoplasmic Igs, and CD20- CD38high surface expression. The present observation should permit the identification of molecules involved in the maturation of B cells into plasma cells, and in their accumulation in rheumatoid synovium.

Antibodies, Monoclonal↗
PubMed1994

Activation of human dendritic cells through CD40 cross-linking.

Dendritic cells, the professional antigen-presenting cells (APC) involved in T cell priming, express CD40, a molecule which triggering plays a key role in B cell growth and differentiation as well as monocyte activation. Herein we demonstrate that dendritic Langerhans cells (D-Lc) generated by culturing cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating and tumor necrosis factor alpha (TNF-alpha) express functional CD40 at a density higher than that found on B cells. Culturing D-Lc on CD40-ligand (CD40L) transfected L cells allowed D-Lc survival as 50 +/- 15% of seeded cells were recovered after 4 d while only 5% survived over control L cells. CD40 activation induced important morphological changes with a reduction of cytoplasmic content and a remarkable increase of dendrite development as well as an altered phenotype. In particular, CD40 triggering induced maintenance of high levels of major histocompatibility complex class II antigens and upregulation of accessory molecules such as CD58, CD80 (B7-1) and CD86 (B7-2). CD40 engagement also seems to turn on D-Lc maturation as illustrated by upregulation of CD25, a molecule usually expressed on interdigitating dendritic cells of secondary lymphoid organs. Finally, CD40 activated D-Lc secreted a limited set of cytokines (TNF-alpha, IL-8, and macrophage inflammatory protein 1 alpha [MIP-1 alpha]) whereas a similar activation induced elutriated monocytes to secrete IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, TNF-alpha, and MIP-1 alpha. As D-Lc activated T cells upregulated CD40L, it is likely that CD40 activation of D-Lc observed herein with a fibroblast cell line stably expressing CD40L, mimics physiological interactions between dendritic cells and T cells.

Adult↗
PubMed1994

Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia cells.

Recent studies have established that interleukin (IL)-10 induces growth and most notably differentiation of normal human B lymphocytes. We studied here the effects of IL-10 on the proliferation and survival of B-chronic lymphocytic leukemia (B-CLL) cells. IL-10 was found to inhibit 54-96% of the spontaneous tritiated thymidine incorporation observed in 3 of 12 B-CLL samples. Furthermore, IL-10 decreased the viable cell recovery of all five B-CLL samples tested, irrespective of whether cells were spontaneously synthesizing DNA or not. After 1 wk, B-CLL populations cultured with IL-10 were lost while those cultured without IL-10 survived. Flow cytometric analysis, DNA gel electrophoresis, and Giemsa staining all revealed that IL-10 induced B-CLL cells to die from apoptosis. This IL-10-mediated apoptosis was dose dependent and specific as it could be inhibited by a neutralizing anti-IL-10 antibody. B-CLL cells undergoing apoptosis in response to IL-10 showed decreased Bcl-2 protein levels. Addition of IL-2, IL-4, interferon gamma, and anti-CD40 monoclonal antibody prevented the IL-10-mediated apoptosis of B-CLL cells. None of the malignant B cell populations obtained from eight non-Hodgkin's lymphomas and three hairy cell leukemias underwent apoptosis after IL-10 treatment, thus suggesting that the apoptotic effect of IL-10 is specific for B-CLL cells. Thus, IL-10 inhibits the DNA synthesis and most notably the survival of B-CLL cells, findings that call for considering IL-10 in the immunotherapy of chemoresistant B-CLL.

Apoptosis↗
PubMed1994

CD40-activated surface IgD-positive lymphocytes constitute the long term IL-4-dependent proliferating B cell pool.

In vitro, B cells undergo long term proliferation when triggered through their CD40 surface molecule and in the presence of IL-4. Here, we show that cells that proliferate in this culture system lose their germinal center (GC) features and acquire or maintain non-GC markers. When separated by the magnetic cell separation system, both sIgD+ and sIgD- B cells can proliferate in this culture system, sIgD+ B cells exhibiting a higher rate of growth than sIgD- cells. Simultaneous flow cytometric measurement of sIgD and DNA content revealed that B lymphocytes can keep their sIgD after entry into cell cycle. Experiments using G8 Id-positive B lymphocytes allowed us to follow the evolution of sIgD+ and sIgD- cells in a reconstituted B cell population. Long term proliferating cells are sIgD+/sIgM(+)-derived B lymphocytes whereas the initial sIgD-/sIgM- cells are lost. Taken together, these data show that anti-CD40 + IL-4 activated sIgD+ B blasts express non-GC characteristics and that sIgD+ B cells preferentially proliferate in the CD40 system. The possible in vivo role of IL-4 + CD40 signaling is discussed.

Antibodies, Monoclonal↗
PubMed1994

The contribution of guanylate cyclase stimulation and K+ channel opening to nicorandil-induced vasorelaxation depends on the conduit vessel and on the nature of the spasmogen.

Nicorandil, the specific K+ channel opener aprikalim, and the stimulant of guanylate cyclase, nitroglycerin, overcame in a concentration-dependent manner the sustained contractile responses evoked by KCl (10-25 mM) and norepinephrine (25-300 nM) in endothelium-denuded rings from rabbit aorta and pulmonary and mesenteric arteries. Nicorandil exhibited similar vasorelaxant potency (EC50, 1.6-3.1 microM) in all preparations investigated. The responses to nicorandil or nitroglycerin for pulmonary artery rings contracted with the two spasmogens and for aorta rings contracted with norepinephrine were not substantially modified by the K+ channel blocker glibenclamide at a concentration (1 microM) that displaced to the right the concentration-response curve to aprikalim obtained with these preparations. However, glibenclamide shifted to the right 2- to 3-fold the concentration-response curve obtained with nicorandil in aorta rings contracted with KCl and in mesenteric artery rings contracted with either KCl or norepinephrine, but not that obtained with nitroglycerin. Methylene blue (5-10 microM), an inhibitor of guanylate cyclase, displaced to the right the control concentration-response curves to nitroglycerin 3- to 21-fold and those to nicorandil 1.5- to 11-fold, but not those to aprikalim. In rabbit mesenteric artery rings, nicorandil both stimulated guanylate cyclase and opened K+ channels, regardless of whether KCl or norepinephrine was used to contract the vessels. However, nicorandil-induced relaxation of the pulmonary artery contracted with these spasmogens and the aorta contracted with norepinephrine was mediated almost entirely by the stimulation of guanylate cyclase, whereas the dual mechanism of action was again demonstrable when the latter vessel was contracted with KCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes.

Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. Herein, we show that IL-10 also promotes DNA synthesis and IgM production by anti-CD40 activated B cell chronic lymphocytic leukemia (B-CLL). Most strikingly, IL-2 and IL-10 were found to synergize to induce the proliferation and differentiation of B-CLL cells. This synergy between IL-2 and IL-10 was also observed with normal B cells which proliferated strongly and secreted large amounts of IgM, IgG, and IgA. The observed synergy is likely to be due to the IL-10-induced increase of high affinity IL-2 receptors on both normal and leukemic B cells. This increase of high affinity receptor is associated to an increase of Tac/CD25 expression that can be detected by flow cytometric analysis. Taken together, these results indicate that IL-10 permits anti-CD40 activated B cells to respond to IL-2 through an induction of high affinity IL-2 receptors. This effect of IL-10 may partly explain how T cells, which activate B cells in a CD40-dependent fashion, induce B cell proliferation and differentiation mostly through IL-2.

B-Lymphocytes↗
PubMed1993

Tumor necrosis factor alpha cooperates with interleukin 3 in the recruitment of a primitive subset of human CD34+ progenitors.

We have recently demonstrated that tumor necrosis factor alpha (TNF-alpha) potentiates interleukin 3 (IL-3) and granulocyte/macrophage colony-stimulating factor-induced growth of CD34+ hematopoietic progenitor cells (HPC), and favors the generation of dendritic/Langerhans cells. The stimulatory effect of TNF-alpha was detailed in the present study. Thus, CD34+ HPC entering in cycle (S/G2M) after a 48-h pulse with IL-3 expressed the transferrin receptor (TfR), and fluorescence-activated cell sorter-separated TfR+ HPC, but not TfR-HPC, showed a high proliferative response to IL-3. In contrast, TfR-HPC were found to undergo strong proliferation in response to IL-3 + TNF-alpha. Limiting dilution experiments indicated that TNF-alpha increased both the frequency and the average size of clones generated from TfR-HPC as a result of the development of a higher number of large clones. In contrast, TNF-alpha did not enhance the IL-3-dependent proliferation of TfR+ HPC. Preculturing CD34+ HPC for 48 h with TNF-alpha enhanced the subsequent generation of IL-3-dependent colony-forming units. Precultures with TNF-alpha or cultures with suboptimal doses of TNF-alpha allowed the recruitment of cells with both granulocytic and monocytic differentiation potential. Taken together, our results indicate that TNF-alpha recruits a subpopulation of CD34+ HPC hyposensitive to IL-3, with high proliferative capacity and some features of multipotential progenitors, that are likely to be more primitive than those responding to IL-3 alone.

Antigens, CD↗
PubMed1993

Slowly progressive apraxia: two case studies.

Two patients with a slowly progressive and severe motor apraxia are presented. In one case, there was only apraxia; in the other there was moderate memory disturbance and a mild decline of global intellectual ability, suggesting a more widespread cognitive dysfunction. In this second case, recognition of the correct use of objects was also severely impaired, suggesting a disturbance of motor knowledge. In both cases, apraxia was asymmetrical, and associated with a contralateral atrophy of the upper parietal cortex, suggesting a differential involvement of separate action systems for each hand.

Aged↗
PubMed1993

Reliability of sampling urine from disposable diapers in elderly incontinent women.

OBJECTIVE: To assess the reliability for biochemical and microbiological analysis of urine collection from disposable diapers in elderly women with severe urinary incontinence. DESIGN: Cross-sectional comparison of two methods of collection. PATIENTS AND MEASUREMENTS: Urine was sampled from 52 women inpatients (aged 68-98 years) in a geriatric hospital ward by pressing a diaper which the patient had worn for 3 hours. Just after this collection, another sample was obtained by retrograde catheterization. Both samples were analyzed for sodium, potassium, chloride, proteins, urea, creatinine, calcium, and phosphate and for cell counts, the presence of bacteria, and bacteria culture. RESULTS: For all the biochemical parameters, the urinary concentrations obtained by the two methods were strongly and significantly correlated. The following differences (mean and range, in mmol/L) were found between the values obtained by the two methods: sodium: 6.05 (-26 to 27), potassium: (-16 to 14), chloride: -1.13 (-24 to 23), urea: 6.85 (-33 to 37), creatinine: 0.24 (-0.95 to 1.45), calcium: -0.22 (-1.27 to 1.70), and phosphate: 2.17 (-2.5 to 13.4). For diagnosis of urinary tract infection, agreement between the two methods was good (kappa = 0.84), and bacteriological agreement was obtained in 25 out of 28 cases (89%). However, for diagnosis of microscopic hematuria, agreement was poor (kappa = 0.50), probably due to the overestimation of the true urinary red cell count in the samples collected by catheterization. CONCLUSION: For routine microbiological and biochemical analysis, urine extraction from disposable diapers is a simple and reasonably reliable method of sampling urine from elderly women with severe incontinence.

Aged↗
PubMed1993

[Extensive fibrous endocarditis as first manifestation of systemic lupus erythematosus].

BACKGROUND: Cardiac abnormalities, such as myocarditis, pericarditis or verrucous endocarditis (Libman-Sacks endocarditis) occur in about one third of patients with systemic lupus erythematosus. This study describes an unusual aspect of endocardial involvement. CASE REPORTS: Case no. 1: A 14 year-old girl was admitted 3 months after acute hemichorea because of heart failure plus biological inflammatory findings. Echocardiography showed mitral insufficiency with enlargement of the left atrium and ventricle. There was some infiltration involving the endocardium of the left ventricle, the chordae tendinae and the mitral valve. The titres of anti-DNA and anti-nuclear antibodies were elevated while the serum hemolytic complement was depressed. Skin biopsy showed IgG, IgM and C1q deposits along the dermoepidermal junction. Corticosteroids, diuretics and vasodilator drugs failed to completely cure the heart failure; the mitral insufficiency required mitral valve replacement 21 months later. Pathological examination showed extended fibrotic changes of the endocardium. Case no. 2: A 4 year-old boy was admitted for acute heart failure due to mitral insufficiency, associated with biological inflammatory findings. Echocardiography showed mitral insufficiency and enlarged left atrium and ventricle. Anti-DNA and anti-nuclear antibody titres were elevated. The patient was given antibiotics followed by corticosteroids and immunosuppressive drugs. The persistence of the mitral insufficiency required mitral valve replacement 7 months later. Pathological examination showed fibrotic changes of the endocardium. Exacerbation of the inflammatory process was seen 2 months after surgery, with development of diffuse proliferative lupus nephritis. The patient died of kidney failure and neurological complications, 44 months after cardiac surgery. CONCLUSION: In both patients, the systemic lupus erythematosus was revealed by endocardial involvement, a complication that is usually seen later. The endocardium changes responsible for mitral insufficiency and requiring valve replacement in these two cases were different from those described as verrucous endocarditis in classical forms of the disease.

Adolescent↗
PubMed1992

Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A.

In the present report, we have investigated the in vitro differentiation of surface(s) sIgD+ and sIgD- human B cells into Ig-secreting cells in response to various stimuli. sIgD+ B cells homogeneously expressed some of the antigens identifying mantle zone B cells, but lacked expression of germinal center markers, thus confirming that the B cell populations positively selected on the basis of sIgD expression were highly enriched for naive B lymphocytes. Conversely, sIgD- B cells expressed some of the antigens specifically associated with germinal center B cells. T cell-independent differentiation of sIgD+ and sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII (CDw32 L cells). In this experimental system, sIgD+ B cells were exclusively proned for IgM synthesis, whereas sIgD- B cells produced IgG, IgM, and IgA. Both the human and viral forms of interleukin 10 (IL-10) strongly increased the Ig secretion by sIgD+ and sIgD- B cells simultaneously activated through sIgs and CD40. IgM and IgG constituted the predominant Ig isotype produced by sIgD+ and sIgD- B cells, respectively, in response to IL-10. sIgD+ B cells could be induced for IgA synthesis upon co-culturing with transforming growth factor beta (TGF-beta) and IL-10, in the presence of an anti-CD40 monoclonal antibody presented by the CDw32 L cells. In contrast, TGF-beta suppressed the IL-10-mediated IgG, IgM, and IgA secretions by sIgD- B cells. sIgD+ B cells could not be induced for IgA synthesis by TGF-beta and IL-10 after crosslinking of their sIgs, suggesting that ligation of CD40 was one of the obligatory signals required for commitment of naive B cells to IgA secretion. Limiting dilution experiments indicated that the IgA-potentiating effect of TGF-beta was due to its capacity to increase the frequency of IgA-producing cells, most likely as a consequence of class switching. Taken together, our data strongly suggest that TGF-beta is involved in the regulation of IgA isotype selection in humans.

Antibody-Producing Cells↗
PubMed1992

Proliferation and differentiation of human CD5+ and CD5- B cell subsets activated through their antigen receptors or CD40 antigens.

The pan-T cell antigen CD5 has been shown to delineate two different mouse B cell subsets, originating from distinct progenitors. In man, on average, 30% of the tonsillar B cell pool expresses this antigen. In the present report, a detailed comparison of the CD5+ and CD5- B cell response to cytokines, following activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken. CD5+ B cells were positively selected by panning or by sorting from tonsils. Two-color immunofluorescence analysis performed on tonsillar B cell populations showed that CD5+ B cells displayed most of the phenotypic features of mantle zone B cells. CD5+ B cells could be stimulated for DNA synthesis by mitogenic concentrations of Staphylococcus aureus, Cowan I strain (SAC), insolubilized anti-IgM antibodies, immobilized anti-CD40 antibodies and phorbol 12-myristate 13-acetate (PMA). The growth-response of small dense CD5- B cells to these T cell-independent mitogens was comparable to that of CD5+ B cells, whereas the low-density, in vivo-activated, CD5- B cells were only marginally stimulated by Ig-cross-linking agents and PMA. Following ligation of sIg, both B cell subsets proliferated essentially in response to interleukin (IL)-2 and IL-4. When used in co-stimulation with immobilized anti-CD40 antibodies, IL-4 promoted growth of CD5+ and CD5- B cells, whereas IL-2 displayed only moderate stimulatory effects. CD5+ and CD5- B cells differentiated into Ig-secreting cells when they were co-cultured with SAC or cross-linked anti-CD40 antibodies and IL-2. However, IgM constituted the major component of the Ig response of CD5+ B cells, whereas high levels of IgG were secreted by CD5- B cells.

Antigens, CD↗
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↗