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      Dynamics of Membrane Trafficking Downstream of B and T Cell Receptor Engagement: Impact on Immune Synapses

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          Abstract

          The onset of an adaptive immune response requires the activation of T and B lymphocytes by antigen-presenting cells, through a specialized form of intercellular communication, known as the immunological synapse (IS). In B lymphocytes the IS promotes efficient recognition and acquisition of membrane-bound Ags, while in T cells, it modulates the T cell response upon exposure to peptide-major histocompatibility complexes. In this review, we highlight the similarities that determine B and T cell activation, focusing on immune receptor downstream signaling events that lead to synapse formation. We stress the notion that polarization of T and B lymphocytes characterized by global changes in cytoskeleton and membrane trafficking modulates synapse structure and function, thus determining lymphocyte effector functions and fate.

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          Most cited references63

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          Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation.

          Exosomes are 60-100-nm membrane vesicles that are secreted into the extracellular milieu as a consequence of multivesicular body fusion with the plasma membrane. Here we determined the protein and lipid compositions of highly purified human B cell-derived exosomes. Mass spectrometric analysis indicated the abundant presence of major histocompatibility complex (MHC) class I and class II, heat shock cognate 70, heat shock protein 90, integrin alpha 4, CD45, moesin, tubulin (alpha and beta), actin, G(i)alpha(2), and a multitude of other proteins. An alpha 4-integrin may direct B cell-derived exosomes to follicular dendritic cells, which were described previously as potential target cells. Clathrin, heat shock cognate 70, and heat shock protein 90 may be involved in protein sorting at multivesicular bodies. Exosomes were also enriched in cholesterol, sphingomyelin, and ganglioside GM3, lipids that are typically enriched in detergent-resistant membranes. Most exosome-associated proteins, including MHC class II and tetraspanins, were insoluble in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS)-containing buffers. Multivesicular body-linked MHC class II was also resistant to CHAPS whereas plasma membrane-associated MHC class II was solubilized readily. Together, these data suggest that recruitment of membrane proteins from the limiting membranes into the internal vesicles of multivesicular bodies may involve their incorporation into tetraspanin-containing detergent-resistant membrane domains.
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            Asymmetric T lymphocyte division in the initiation of adaptive immune responses.

            A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.
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              Antigen receptor tail clue.

              M. RETH (1989)
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                Author and article information

                Journal
                Traffic
                tra
                Traffic (Copenhagen, Denmark)
                Blackwell Publishing Ltd
                1398-9219
                1600-0854
                June 2009
                18 March 2009
                22 April 2009
                : 10
                : 6
                : 629-636
                Affiliations
                simpleINSERM U932, Institut Curie 12 rue Lhomond, 75005, Paris, France
                Author notes
                *Corresponding author: Ana-Maria Lennon-Duménil, Ana-Maria.Lennon@ 123456curie.fr
                Article
                10.1111/j.1600-0854.2009.00913.x
                2723867
                19416472
                abe2a2c8-1c29-44a7-80a6-e3826b51c8ef
                Journal compilation © 2009 Blackwell Munksgaard

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 22 December 2008
                : 12 March 2009
                Categories
                Review Articles

                Sociology
                membrane trafficking,immune synapse,cytoskeleton,b cell receptor,polarity,t cell receptor
                Sociology
                membrane trafficking, immune synapse, cytoskeleton, b cell receptor, polarity, t cell receptor

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