Cytokines in adult respiratory distress syndrome.
Explore the source record for details and available documents.
Bronchoalveolar Lavage Fluid↗
Biomedical subjects
F Rousset
Publications and source records attributed to F Rousset.
Human monoclonal autoantibodies specific for the bullous pemphigoid antigen 1 (BPAg 1).
Bullous pemphigoid (BP) is an acquired blistering skin disease associated with the production of IgG autoantibodies to the 230-kDa BP Ag (BPAg1). To better characterize the epitopes of BPAg1, we generated immortalized B cell lines secreting human mAbs (HumAbs) to BPAg1 from two BP patients whose sera reacted with native BPAg1 but not with a recombinant BP55 carboxyl-terminal peptide. Ab-producing B cell lines were established by EBV infection of CD40-activated PBMCs. Three independent clonal lines were obtained that secreted IgG HumAbs, including one IgG1 kappa (BP3) and two distinct IgG4 kappa (BP1 and BP2). These three HumAbs immunoprecipitated BPAg1. Blocking immunofluorescence experiments and phylogenetic studies showed that these Abs recognize different epitopes of BPAg1. This analysis with HumAbs further extends the serologic demonstration of the wide variety of epitopes recognized by BPAg1 autoantibodies which contrasts with the limited number of epitopes recognized by thyroid peroxidase monoclonal autoantibodies.
Antibodies, Monoclonal↗
Regulatory effects of prostaglandin E2 on the growth and differentiation of human B lymphocytes activated through their CD40 antigen.
We have studied the effects of prostaglandin E2 (PGE2) on the growth and differentiation of human tonsillar B lymphocytes cultured in the CD40 system with or without IL-4 or IL-10. PGE2 (10(-9) to 10(-6) M) enhanced proliferation of B cells activated through their CD40 Ag, but not their Ig secretion. PGE2 further potentiated both IL-4- and IL-10-induced B cell growth as determined by [3H]TdR uptake and cellular enumeration. The IL-10-induced IgM, IgG, and IgA secretion was enhanced twofold to fourfold after addition of PGE2, whereas IL-4-induced IgG and IgE secretion was inhibited. The IgE production was particularly sensitive as an approximately 90% inhibition was obtained for 10(-7) M PGE2. In addition, PGE2 inhibited IgE production by naive surface IgD+ B cells cultured in the CD40 system, suggesting that PGE2 may interact with mechanisms involved in IgE switching. PGE2 displayed similar effects on cytokine-induced proliferation and Ig secretion of B cells activated by anti-CD40 Abs used in a soluble form. Finally, the PGE2 effects were mimicked by agents increasing cAMP, indicating that the PGE2 activities are likely to depend on the activation of the cAMP pathway. Altogether, the present data indicate that PGE2 stimulates human CD40-activated B cell growth, but differently modulates cytokine-induced differentiation. Thus, in microenvironments supporting the development of an immune response, the secretion of PGE2 by competent cells such as macrophages may participate in the regulation of the humoral response.
Antigens, CD↗
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↗
Expression of Bruton's tyrosine kinase protein within the B cell lineage.
Defects in the gene encoding Bruton's tyrosine kinase (Btk), normally expressed in B cells, cause X-linked agammaglobulinemia (XLA). The phenotype of XLA is characterized by a lack of circulating B cells and immunoglobulin. It has been suggested that B cell maturation from the pre-B cell stage to more mature stages is dependent on the appropriate expression of this gene. The Btk mRNA is expressed in B cells and myeloid cells, but protein expression in relation to B cell maturation has not been determined. Moreover, expression of the Btk protein has so far only been investigated in human Epstein-Barr virus-transformed B cell lines, and in murine splenocytes and B cell lines. We have developed an antiserum which recognizes the human Btk protein and shown that normal human tonsillar B cells, peripheral blood monocytes and myeloid cells express the protein, whereas tonsil-derived T cells do not. We also show that the protein is present in early and mature human B cell lines, but is absent in terminally differentiated plasma cell lines. Furthermore, expression is reduced or absent in three B lineage cell lines derived from two patients with defined genetic mutations in Btk and suffering from XLA.
Agammaglobulinaemia Tyrosine Kinase↗
Molecular control of B lymphocyte growth and differentiation.
During antigen driven immune responses, antigen-specific naive B lymphocytes undergo a cascade of events including activation, expansion, mutations, isotype switch, selections and differentiation into either antibody secreting plasma cells or memory B cells. These antigen-dependent events, which we propose to call immunopoiesis, occur in different areas of secondary lymphoid organs, as well as other nonlymphoid organs. B cells interact with antigens and numerous cell types (T cells, dendritic cells, follicular dendritic cells and macrophages) through numerous cell surface molecules and cytokines. B cells costimulated through their antigen receptor and cytokines such as interleukin 2 (IL-2), IL-4 and IL-10 undergo limited proliferation and differentiation into immunoglobulin (Ig) secreting cells. In contrast, crosslinking of the B cell CD40 antigen, a member of the tumor necrosis factor (TNF) receptor family, results in major cellular activation further modulated by cytokines. In particular, IL-4 and IL-13 permit establishment of long-term factor-dependent B cell lines, as well as isotype switch towards the production of IgE and IgG4. Addition of IL-10 to CD40-activated B cells results in limited proliferation and remarkable differentiation into plasma cells. IL-10 also participates in isotype switch towards IgG1, IgG3 and IgA. The ligand for CD40, a member of the TNF family, is transiently expressed on activated T cells, and interrupted CD40/CD40-L interactions result in profoundly altered humoral immune responses.
Animals↗
Properties of Drosophila simulans strains experimentally infected by different clones of the bacterium Wolbachia.
Maternally inherited bacteria of the genus Wolbachia are responsible for reproductive incompatibilities between strains of Drosophila simulans. Such incompatibilities are known in several types of crosses, including both directions of crossing between two types of infected strains, 'R' and 'S'. To determine whether the bidirectional incompatibility between R and S flies is due only to differences between their bacteria, flies from an uninfected strain have been experimentally infected with bacteria associated with each type. The incompatibility properties of experimental strains are close to those of original strains harbouring the same bacteria and therefore independent of nuclear background. Backcross experiments, however, show that the infection level of a strain depends on the nature of paternal ancestors. This is not explained by nuclear effects but is possibly the result of an interaction between the infection levels of both parents, in which the infection level of S strains is an equilibrium between a tendency for females to produce weakly infected offspring and selection of more infected eggs by sperm from infected males.
Animals↗
High levels of circulating IL-10 in human malaria.
IL-10 is a monocyte/lymphocyte derived cytokine which has been shown to inhibit certain cellular immune responses such as delayed hypersensitivity. In particular, the production of tumour necrosis factor (TNF), IL-1 and IL-6, which are involved in malaria pathology, are strongly inhibited by IL-10. Accordingly, we examined whether IL-10 could be involved in a human acute parasitic infection such as Plasmodium falciparum malaria. Human IL-10 levels in plasma were determined by two-site ELISA method, taking care to avoid non-specific reactions due to autoantibodies. Fourteen cerebral, 11 severe, and 20 mild malaria cases had mean IL-10 levels of 2812, 2882 and 913 pg/ml, respectively, while 98% of healthy individuals had undetectable (less than 100 pg/ml) circulating IL-10. Thirteen of the 25 cerebral/severe cases had > 2000 pg/ml. In 11 hospitalized patients, circulating IL-10 levels were found to return to virtually normal levels 7 days after antimalarial chemotherapy when biological and clinical malaria features had disappeared (mean levels fell from 3880 to 333 pg/ml). Further studies are required to determine whether these elevated levels of IL-10 play a beneficial role by reducing the parasite-induced inflammatory response, or a detrimental one by decreasing the cellular immune responses.
Adolescent↗
The CD40 antigen and its ligand.
CD40 is an integral membrane protein found on the surface of B lymphocytes, dendritic cells, follicular dendritic cells, hematopoietic progenitor cells, epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor necrosis factor receptor superfamily. The CD40 gene maps to human chromosome 20q11-2-q13-2. CD40 binds to a ligand (CD40-L) which is an approximately 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is expressed on activated T cells, mostly CD4+ but also some CD8+ as well as basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome. Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the generation of factor-dependent long-term normal human B cell lines and the secretion of IgE following isotype switching. Addition of IL-10 results in very high immunoglobulin production with limited cell proliferation. IL-10 induces naive B cells to produce IgG3, IgG1, and IgA1, and further addition of TGF beta permits the secretion of IgA2. Several evidences suggest that CD40-dependent activation of B cells is important for the generation of memory B cells within the germinal centers: (i) CD40 activated germinal center B cells cultured in the presence of IL-4 acquire a memory B cell phenotype, (ii) CD40 activated B cells can undergo isotype switching, (iii) the deficit of CD40-L results in the hyper-IgM syndrome characterized by lack of germinal centers in secondary lymphoid organ follicles and lack of IgG, IgA, and IgE, and (iv) CD40-L positive T cells are present in secondary follicles. Thymic epithelial cells, activated monocytes, and dendritic cells express CD40 antigen which may be involved in an enhanced cytokine production by these cells, allowing an amplification of T cell proliferation. Finally, as other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.
Amino Acid Sequence↗
Human interleukin 4.
Human IL-4 is a mature glycoprotein of 129 amino acids, mostly secreted by activated T cells. It is a pleiotropic cytokine which acts on T and B lymphocytes, monocytes, polymorphonuclears, 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 amino acids which is a member of the newly described hematopoietin receptor superfamily. IL-4 may prove useful as an anti-tumoral and anti-inflammatory agent.
B-Lymphocytes↗
Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor.
Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL-10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.
Adolescent↗
Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10.
Interleukin 10 (IL-10) is a pleiotropic factor that enhances proliferation of activated human B lymphocytes and induces them to secrete high amounts of immunoglobulins. Here we show that several human B cell lines were able to constitutively secrete human (h)IL-10. Whereas none of the pre-B nor the plasmocytic cell lines tested produced hIL-10, 25 of the 36 tested mature B cell lines (lymphoblastoid and Burkitt lymphoma cell lines) secreted hIL-10. Moreover, 24 of these 25 hIL-10-producing B cell lines contained the Epstein-Barr virus (EBV) genome, suggesting a relationship between hIL-10 production by human B cell lines and EBV expression. Accordingly, whereas polyclonal activation via triggering of surface immunoglobulins or CD40 antigen induced highly purified normal human B lymphocytes to produce only low (0.3-0.4 ng/ml) but significant amounts of hIL-10, EBV infection induced them to secrete high amounts of hIL-10 (4-9 ng/ml). Furthermore, addition of exogenous hIL-10, simultaneously to EBV infection, potentiated cell proliferation, whereas a blocking anti-IL-10 antiserum inhibited it. Thus, hIL-10 produced by infected human B lymphocytes appears to be involved in the mechanisms of EBV-induced B cell proliferation.
B-Lymphocytes↗
Induction by anti-CD40 antibody or soluble CD40 ligand and cytokines of IgG, IgA and IgE production by B cells from patients with X-linked hyper IgM syndrome.
We studied the ability of B lymphocytes from patients with X-linked hyper IgM syndrome (HIGM1) to be activated via the CD40 membrane receptor. HIGM1 is caused by a CD40 ligand gene mutation, leading to defective expression on the membrane of activated T lymphocytes. We found that triggering of B cells by an anti-CD40 monoclonal antibody or the soluble CD40 ligand plus interleukin (IL)-4 or IL-10 led to B cell proliferation and/or differentiation towards IgG, IgA and IgE secretion. This was reflected by transcription of C gamma, alpha and epsilon membrane isotype expression and IgG, IgA and IgE production. These results confirm the integrity of B cells in patients with the HIGM1 immunodeficiency and open up new therapeutic possibilities.
Antibodies, Monoclonal↗
The reproductive incompatibility system in Drosophila simulans: DAPI-staining analysis of the Wolbachia symbionts in sperm cysts.
Any hitherto available technique used to detect the presence of Wolbachia, a rickettsia-like endosymbiont of Drosophila simulans, i.e., crossing with tester strains, electron microscope observations, DAPI-staining of embryo, or amplification of specific sequences by PCR are notably time-consuming techniques. Staining sperm cysts with the fluorochrome DAPI is here shown to be a fast and reliable technique to detect the symbiont and evaluate the level of infection of individual males. Wolbachia cells are abundant in sperm cysts and make up a mass which is eliminated in the waste bag during spermatogenesis. Such a mass was absent in all those strains known to be aposymbiotic. In infected strains, tetracycline treatment led to the disappearance of the symbionts within sperm cysts. In aging males, a decrease in the proportion of infected cysts were observed. There was however no apparent change in the number of symbionts in the cysts which remained infected. The reduction of reproductive incompatibility, which is observed in older males, may be explained by this process, i.e., a decrease in the frequency of infected cysts.
Aging↗
Role of cytokines in human B lymphocyte growth and differentiation.
B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (Fc gamma RII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 to such cultures results in the generation of factor dependent long-term normal human B cell lines and in the secretion of IgE following isotype switching. Addition of IL-10 results in limited cell proliferation but most importantly in very high immunoglobulin production which results from the differentiation of B cells into plasma cells. The combination of IL-10 and TGF beta induces naive sIgD+ sIgM+ B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a 32 kDa glycoprotein transiently expressed on activated T cells. This interaction of the CD40 antigen on B cells with its ligand on T cells represents a key step in T cell dependent B cell activation.
Animals↗
IL-10 and IL-13 as B cell growth and differentiation factors.
B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (Fc gamma RII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 or IL-13 result in the proliferation of human B cells and in the secretion of IgE following isotype switching. Addition of IL-10 permits limited cell proliferation but most importantly results in very high immunoglobulin production following differentiation of B cells into plasma cells. In response to IL-10, unseparated B cells cultured in the CD40 system produced the four IgG subclasses in ratio comparable to those observed in the serum. IL-10 induces naive B cells to secrete low but reproducible amounts of IgG and IgA. The combination of IL-10 and TGF beta induces naive B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a ligand transiently expressed on activated T cells. This interaction of the CD40 antigen on B cells with its counter-structure on T cells represents a key step in T cell dependent B cell activation.
Antigens, CD↗
Wolbachia endosymbionts responsible for various alterations of sexuality in arthropods.
Rickettsia-like maternally inherited bacteria have been shown to be involved in a variety of alterations of arthropod sexuality, such as female-biased sex ratios, parthenogenesis, and sterility of crosses either between infected males and uninfected females or between infected individuals (cytoplasmic incompatibility). We have characterized several of these microorganisms through partial sequences of the small (16S) and large (23S) subunit ribosomal DNA. All the symbionts identified, which include several cytoplasmic incompatibility microorganisms, several endosymbionts of terrestrial isopods, and symbionts of two thelytokous Trichogramma wasp species, belong to a monophyletic group of related symbionts, some of which have previously been detected in several insects exhibiting cytoplasmic incompatibility. Three molecular lineages can be identified on the basis of 16S as well as 23S sequences. Although they are only known as endocellular symbionts, Wolbachia spread by horizontal transfer across host lineages as evidenced by their diversification which occurred long after that of their hosts, and by the non-congruence of the phylogenetic relationships of symbionts and their hosts. Indeed, symbionts of two different lineages have been found in the same host species, whereas closely related endosymbionts are found in distinct insect orders. Isopod endosymbionts form a separate lineage, and they can determine feminization as well as cytoplasmic incompatibility. The ability to determine cytoplasmic incompatibility, found in all lineages, is probably ancestral to this group.
Animals↗
Molecular identification of Wolbachia, the agent of cytoplasmic incompatibility in Drosophila simulans, and variability in relation with host mitochondrial types.
Sequences of a segment of the 16S ribosomal DNA of Wolbachia, a rickettsia-like microorganism responsible for cytoplasmic incompatibility in Drosophila simulans, have been obtained after polymerase chain reaction (PCR) amplification. Their comparison with other eubacterial sequences allows us to assign these endosymbionts to the alpha subdivision of purple bacteria. Four related sequences have been obtained for microorganisms carried by eight isofemale lines representative of the three mitochondrial types of D. simulans. Their phylogeny and level of divergence do not parallel that of the mitochondrial DNA, suggesting that several independent infections occurred. There is no direct relation between bacterial phylogeny and formerly identified incompatibility types.
Animals↗