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71.
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R V Gilden J Kern A E Freeman C E Martin R C McAllister H C Turner R J Huebner 《Nature》1968,219(5153):517-518
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ICOS is critical for CD40-mediated antibody class switching 总被引:58,自引:0,他引:58
McAdam AJ Greenwald RJ Levin MA Chernova T Malenkovich N Ling V Freeman GJ Sharpe AH 《Nature》2001,409(6816):102-105
The inducible co-stimulatory molecule (ICOS) is a CD28 homologue implicated in regulating T-cell differentiation. Because co-stimulatory signals are critical for regulating T-cell activation, an understanding of co-stimulatory signals may enable the design of rational therapies for immune-mediated diseases. According to the two-signal model for T-cell activation, T cells require an antigen-specific signal and a second, co-stimulatory, signal for optimal T-cell activation. The co-stimulatory signal promotes T-cell proliferation, lymphokine secretion and effector function. The B7-CD28 pathway provides essential signals for T-cell activation, but does not account for all co-stimulation. We have generated mice lacking ICOS (ICOS-/- ) to determine the essential functions of ICOS. Here we report that ICOS-/- mice exhibit profound deficits in immunoglobulin isotype class switching, accompanied by impaired germinal centre formation. Class switching was restored in ICOS-/- mice by CD40 stimulation, showing that ICOS promotes T-cell/B-cell collaboration through the CD40/CD40L pathway. 相似文献
76.
Direct evidence for extensive paternal mitochondrial DNA inheritance in the marine mussel Mytilus. 总被引:17,自引:0,他引:17
Inheritance of mitochondrial DNA in animals was thought to be strictly maternal. Recently, evidence for incidental paternal mtDNA leakage was obtained in hybrid crosses of Drosophila and mice. In mice, the frequency of paternal mtDNA contributions was estimated at 10(-4), compared with maternal contributions. The common occurrence in the marine mussel Mytilus of heteroplasmic individuals with two or more types of highly diverged mtDNA molecules was interpreted as strong evidence for biparental mtDNA inheritance by some, but not by others. We report here results from pair-matings involving two species of mussels, Mytilus edulis and Mytilus trossulus. Extensive contribution of paternal mtDNA, amounting to several orders of magnitude higher than that inferred for Drosophila or mice, was observed in both intra- and interspecific crosses. 相似文献
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Signalling through the MHC class II cytoplasmic domain is required for antigen presentation and induces B7 expression. 总被引:27,自引:0,他引:27
Class II major histocompatibility complex (MHC) molecules function as antigen-presenting elements as well as signal transducers on B lymphocytes. We previously reported that a B lymphoma cell transfectant, 5C2, expressing genetically engineered I-Ak molecules with truncated cytoplasmic domains was severely impaired in both antigen presentation and in anti-Ia-induced intracytoplasmic signalling. These two functions could be restored by preculturing 5C2 cells with cyclic AMP analogues. Here we demonstrate that impaired signal transduction by truncated class II molecules results in a deficiency in induction of the newly defined B-cell accessory molecule B7 (ref. 8), which can be reversed by restoration of B7 expression. These data imply that contact of the T-cell antigen receptor with MHC/antigen ligand results in signal transmission through the class II cytoplasmic domain. This signal, which can be mimicked by dibutyryl cAMP, induces expression of B7, resulting in effective antigen presentation. The fact that crosslinking of surface class II MHC also induces B7 expression on normal resting human B cells supports this contention. 相似文献
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B. M. Freeman 《Cellular and molecular life sciences : CMLS》1972,28(6):696-697
Résumé Des poussins boursectomisés traités avec du plasma de poussins intacts ne subissent pas de perte de réponse glycémique à l'insuline, mesurée d'après les changements de niveaux du glucose dans le plasma sanguin. Il est suggéré que les résultats sont compatibles avec l'hypothèse selon laquelle la bourse de Fabricius est une glande endocrine. 相似文献
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Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils 总被引:62,自引:0,他引:62
The macrophage scavenger receptor is a trimeric membrane glycoprotein with unusual ligand-binding properties which has been implicated in the development of atherosclerosis. The trimeric structure of the bovine type I scavenger receptor, deduced by complementary DNA cloning, contains three extracellular C-terminal cysteine-rich domains connected to the transmembrane domain by a long fibrous stalk. This stalk structure, composed of an alpha-helical coiled coil and a collagen-like triple helix, has not previously been observed in an integral membrane protein. 相似文献