The Experts below are selected from a list of 23643 Experts worldwide ranked by ideXlab platform
Bobby H Gaspar - One of the best experts on this subject based on the ideXlab platform.
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the c76r transmembrane activator and calcium modulator cyclophilin ligand interactor mutation disrupts antibody Production and b cell homeostasis in heterozygous and homozygous mice
The Journal of Allergy and Clinical Immunology, 2011Co-Authors: Chiara Bacchelli, Sylvie Buckridge, Karen F Buckland, Pascal Schneider, Adrian J Thrasher, Bobby H GasparAbstract:Background Mutations in TNFRSF13B , the gene encoding transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), are found in 10% of patients with common variable immunodeficiency. However, the most commonly detected mutation is the heterozygous change C104R, which is also found in 0.5% to 1% of healthy subjects. The contribution of the C104R mutation to the B-cell defects observed in patients with common variable immunodeficiency therefore remains unclear. Objective We sought to define the functional consequences of the C104R mutation on B-cell function. Methods We performed in vitro studies of TACI C104R expression and signaling. A knock-in mouse with the equivalent mutation murine TACI (mTACI) C76R was generated as a physiologically relevant model of human disease. We examined homozygous and heterozygous C76R mutant mice alongside wild-type littermates and studied specific B-cell lineages and antibody responses to T cell–independent and T cell–dependent challenge. Results C104R expression and ligand binding are significantly diminished when the mutant protein is expressed in 293T cells or in patients' cell lines. This leads to defective nuclear factor κB activation, which is proportionally restored by reintroduction of wild-type TACI. Mice heterozygous and homozygous for mTACI C76R exhibit significant B-cell dysfunction with splenomegaly, marginal zone B-cell expansion, diminished Immunoglobulin Production and serological responses to T cell–independent antigen, and abnormal Immunoglobulin synthesis. Conclusions These data show that the C104R mutation and its murine equivalent, C76R, can significantly disrupt TACI function, probably through haploinsufficiency. Furthermore, the heterozygous C76R mutation alone is sufficient to disturb B-cell function with lymphoproliferation and Immunoglobulin Production defects.
Adrian J Thrasher - One of the best experts on this subject based on the ideXlab platform.
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the c76r transmembrane activator and calcium modulator cyclophilin ligand interactor mutation disrupts antibody Production and b cell homeostasis in heterozygous and homozygous mice
The Journal of Allergy and Clinical Immunology, 2011Co-Authors: Chiara Bacchelli, Sylvie Buckridge, Karen F Buckland, Pascal Schneider, Adrian J Thrasher, Bobby H GasparAbstract:Background Mutations in TNFRSF13B , the gene encoding transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), are found in 10% of patients with common variable immunodeficiency. However, the most commonly detected mutation is the heterozygous change C104R, which is also found in 0.5% to 1% of healthy subjects. The contribution of the C104R mutation to the B-cell defects observed in patients with common variable immunodeficiency therefore remains unclear. Objective We sought to define the functional consequences of the C104R mutation on B-cell function. Methods We performed in vitro studies of TACI C104R expression and signaling. A knock-in mouse with the equivalent mutation murine TACI (mTACI) C76R was generated as a physiologically relevant model of human disease. We examined homozygous and heterozygous C76R mutant mice alongside wild-type littermates and studied specific B-cell lineages and antibody responses to T cell–independent and T cell–dependent challenge. Results C104R expression and ligand binding are significantly diminished when the mutant protein is expressed in 293T cells or in patients' cell lines. This leads to defective nuclear factor κB activation, which is proportionally restored by reintroduction of wild-type TACI. Mice heterozygous and homozygous for mTACI C76R exhibit significant B-cell dysfunction with splenomegaly, marginal zone B-cell expansion, diminished Immunoglobulin Production and serological responses to T cell–independent antigen, and abnormal Immunoglobulin synthesis. Conclusions These data show that the C104R mutation and its murine equivalent, C76R, can significantly disrupt TACI function, probably through haploinsufficiency. Furthermore, the heterozygous C76R mutation alone is sufficient to disturb B-cell function with lymphoproliferation and Immunoglobulin Production defects.
Raif S Geha - One of the best experts on this subject based on the ideXlab platform.
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transmembrane activator calcium modulator and cyclophilin ligand interactor drives plasma cell differentiation in lps activated b cells
The Journal of Allergy and Clinical Immunology, 2009Co-Authors: Esra Ozcan, Lilit Garibyan, John Lee, Richard J Bram, Kongpeng Lam, Raif S GehaAbstract:Background Transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) expression on B cells is upregulated by Toll-like receptor (TLR) 4. Objective We sought to examine whether TACI synergizes with TLR4 in driving Immunoglobulin Production by B cells and to examine the mechanism of this synergy. Methods Purified mouse naive B cells were stimulated with the TACI ligand a proliferation-inducing ligand (APRIL) and with suboptimal concentrations of the TLR4 ligand LPS in the presence or absence of IL-4. Immunoglobulin secretion was measured by means of ELISA. Surface IgG1–positive B cells and CD138 + plasmacytoid cells were enumerated by means of FACS. Expression of γ1 and e germline transcripts, activation-induced cytidine deaminase, and γ1 and e mature transcripts was measured by means of RT-PCR. Results APRIL synergized with LPS in driving B-cell proliferation and IgM, IgG1, IgG3, IgE, and IgA Production. This was mediated by TACI because it was preserved in B-cell maturation antigen −/− , but not TACI −/− , B cells. APRIL and LPS synergized to promote isotype switching, as evidenced by increased expression of activation-induced cytidine deaminase and γ1 and e mature transcripts and generation of surface IgG1–positive cells. More importantly, APRIL and LPS strongly synergized to drive the plasma cell differentiation program, as evidenced by an increase in CD138 + cells and expression of B lymphocyte induced maturation protein-1 (Blimp-1), interferon regulatory factor-4 (IRF-4), and the spliced form of X-box binding protein-1 (XBP-1). TACI −/− mice had impaired IgM and IgG1 antibody responses to immunization, with a suboptimal dose of the type I T cell–independent antigen 2, 4, 6- Trinitrophenol (TNP)-LPS. Conclusions These observations suggest that TACI cooperates with TLR4 to drive B-cell differentiation and Immunoglobulin Production in vitro and in vivo .
Michihiro Sugano - One of the best experts on this subject based on the ideXlab platform.
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effect of tea extracts and phenolic components on Immunoglobulin Production by mesenteric lymph node lymphocytes of sprague dawley rats
Food Science and Technology International Tokyo, 1997Co-Authors: Koji Yamada, Shihoko Kaku, Nasra Hassan, Takashi Watanabe, Michihiro SuganoAbstract:We examined the effect of tea extracts on Immunoglobulin (Ig) Production of mesenteric lymph node lymphocytes of Sprague-Dawley rats and found that various extracts suppressed the Production of IgA, IgG, and IgM. In addition, the original extracts of green and black teas strongly enhanced IgE Production, and their 102 or 103 times diluted samples exerted an inhibitory effect. Similarly, tea polyphenols having a triphenol group enhanced IgE Production at 1 mM and inhibited it at concentrations below 100 μM. On the contrary, diphenolic epicatechin did not affect IgE Production. Though all tea polyphenols exerted inhibitory effect on the Production of IgA and IgG at concentrations above 10 μM, triphenolic compounds, such as epigallocatechin gallate, gallic acid and pyrogallol, exerted an enhancing tendency on IgA Production at 0.1 μM. These results suggest that the Ig Production-regulating activity of tea extract is partly due to tea polyphenols, especially those having a triphenol group.
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Effect of Vegetable Extracts on Immunoglobulin Production by Mesenteric Lymph Node Lymphocytes of Sprague-Dawley Rats
Bioscience Biotechnology and Biochemistry, 1997Co-Authors: Shihoko Kaku, Koji Yamada, Nasra Hassan, Takashi Watanabe, Michihiro SuganoAbstract:To clarify the Immunoglobulin Production-regulating activity of vegetable extracts, mesenteric lymph node lymphocytes of Sprague-Dawley rats were cultured in the presence of 25 different vegetable extracts. The Immunoglobulin content in the culture medium determined by ELISA indicated that the lily family (Liliaceae) vegetables most strongly enhanced the Production of IgA and IgG, whereas they suppressed IgE Production.
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effect of unsaturated fatty acids and antioxidants on Immunoglobulin Production by mesenteric lymph node lymphocytes of sprague dawley rats
Journal of Biochemistry, 1996Co-Authors: Koji Yamada, Beong Ou Lim, Pham Hung, Kazunari Yoshimura, Saburo Taniguchi, Michihiro SuganoAbstract:The effect of UFA on Ig Production by rat MLN lymphocytes was examined to clarify their influence on allergic reactions. A 4-h treatment at 1 mM inhibited the Production of IgA, IgG, and IgM by the lymphocytes, but stimulated IgE Production. The IgE Production-stimulating activity became stronger with increasing number of carbon atoms and/or double bonds. However, no saturated fatty acid with carbon numbers from 12 to 18 affected IgE Production by the lymphocytes. Hydrogen peroxide exerted Ig Production-regulating activity similar to that of UFA, suggesting that the effect of UFA is at least partly due to oxidation products. Thus, the effect of antioxidants on the Ig Production-regulating activity of arachidonic acid was examined. alpha-Tocopherol and BHT annulled the stimulation of IgE Production by arachidonic acid, but ascorbic acid was not effective. The IgE Production-enhancing activity of UFA was closely related to their oxidation rate in culture medium. These results suggest that UFA enhance the allergic reaction through the stimulation of IgE Production and the inhibition of IgA Production, and that hydrophobic antioxidants are partially effective to annul the adverse effect of UFA.
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Effects of bile acids and lectins on Immunoglobulin Production in rat mesenteric lymph node lymphocytes
In Vitro Cellular & Developmental Biology - Animal, 1994Co-Authors: Beong Ou Lim, Koji Yamada, Michihiro SuganoAbstract:We investigated the effect of bile acids either alone or in combination with lectins on Immunoglobulin (Ig) Production in vitro of rat mesenteric lymph node (MLN) lymphocytes to examine their immunoregulatory activities. Among free bile acids examined, chenodeoxycholic acid stimulated IgE Production by MLN lymphocytes and inhibited IgA Production at the concentration of 0.3 m M , whereas cholic and deoxycholic acids exerted the comparable effect at 3 m M . Among conjugated bile acids, deoxycholic acid derivatives stimulated IgE Production more strongly than cholic acid derivatives. On the other hand, free and conjugated bile acids did not affect IgG Production. The IgE Production by MLN lymphocytes was stimulated by concanavalin A and inhibited by pokeweed mitogen, and the effect of phytohemmagglutinin and lipopolysaccharide was marginal. These lectins did not affect IgA and IgG Production by the lymphocytes. In the presence of lectins, free bile acids affected IgE Production at 0.03 m M . These results suggest the possibility that bile acid is a stimulant for food allergy.
Chiara Bacchelli - One of the best experts on this subject based on the ideXlab platform.
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the c76r transmembrane activator and calcium modulator cyclophilin ligand interactor mutation disrupts antibody Production and b cell homeostasis in heterozygous and homozygous mice
The Journal of Allergy and Clinical Immunology, 2011Co-Authors: Chiara Bacchelli, Sylvie Buckridge, Karen F Buckland, Pascal Schneider, Adrian J Thrasher, Bobby H GasparAbstract:Background Mutations in TNFRSF13B , the gene encoding transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), are found in 10% of patients with common variable immunodeficiency. However, the most commonly detected mutation is the heterozygous change C104R, which is also found in 0.5% to 1% of healthy subjects. The contribution of the C104R mutation to the B-cell defects observed in patients with common variable immunodeficiency therefore remains unclear. Objective We sought to define the functional consequences of the C104R mutation on B-cell function. Methods We performed in vitro studies of TACI C104R expression and signaling. A knock-in mouse with the equivalent mutation murine TACI (mTACI) C76R was generated as a physiologically relevant model of human disease. We examined homozygous and heterozygous C76R mutant mice alongside wild-type littermates and studied specific B-cell lineages and antibody responses to T cell–independent and T cell–dependent challenge. Results C104R expression and ligand binding are significantly diminished when the mutant protein is expressed in 293T cells or in patients' cell lines. This leads to defective nuclear factor κB activation, which is proportionally restored by reintroduction of wild-type TACI. Mice heterozygous and homozygous for mTACI C76R exhibit significant B-cell dysfunction with splenomegaly, marginal zone B-cell expansion, diminished Immunoglobulin Production and serological responses to T cell–independent antigen, and abnormal Immunoglobulin synthesis. Conclusions These data show that the C104R mutation and its murine equivalent, C76R, can significantly disrupt TACI function, probably through haploinsufficiency. Furthermore, the heterozygous C76R mutation alone is sufficient to disturb B-cell function with lymphoproliferation and Immunoglobulin Production defects.
