[{"key":"dc.contributor.author","value":"Jang, Caren Lynn","language":null},{"key":"dc.date.accessioned","value":"2009-03-09T16:48:20Z","language":null},{"key":"dc.date.available","value":"2009-03-09T16:48:20Z","language":null},{"key":"dc.date.issued","value":"2008","language":null},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/5747","language":null},{"key":"dc.description.abstract","value":"The B cell antigen receptor (BCR) is expressed on the surface of B lymphocytes where it can\nbind antigen then transmit signals which regulate activation, growth, and differentiation. These\nsignals can induce a number of cytoskeletal rearrangements leading to changes in adherence,\nspreading, polarity, immune synapse formation, migration and internalization. In the latter\nsituation, BCR internalization results in the uptake of antigen which can then be processed and\npresented to T cells on MHC II. The relative importance of regions within the Ig\u03b1 and Ig\u03b2\ncytoplasmic domains have been studied in terms of signaling but their roles in BCR\ninternalization and trafficking are less clear. We hypothesize that the structure of Ig\u03b1 and Ig\u03b2\ncytoplasmic domains is important for normal BCR internalization and trafficking. An Ig\u03b1 and\nIg\u03b2 deficient lymphoid cell line has been used to express mIgM along with a panel of Ig\u03b1 and\nIg\u03b2 mutants in order to compare their internalization and subcellular localization in both a\nqualitative and quantitative manner. Using this system it was shown that the Ig\u03b1 and Ig\u03b2\ncytoplasmic domains are each sufficient for internalization and that the internalization signal is\ncontained in a region past the first tyrosine residue on either chain, Y176 and Y195 respectively.\nIt was also determined that the Ig\u03b1 cytoplasmic domain makes a larger contribution to\ninternalization than the Ig\u03b2 tail and that a 4 amino acid motif normally contained within the Ig\u03b1\nITAM is sufficient to allow internalization. In terms of receptor trafficking it was shown that\neach cytoplasmic domain is sufficient for trafficking to lysosomal compartments but that a\nnormal rate of trafficking likely requires the tandem effects of both Ig\u03b1 and Ig\u03b2. It was also\nshown that BCR-induced signaling is generally reduced in mutants with an Ig\u03b1 truncation or an\nIg\u03b2 duplication, but that the Ig\u03b1 truncation results in an increased and sustained level of ERK\nphosphorylation. Further studies with the panel of mutants will determine the role of Ig\u03b1 and Ig\u03b2\nstructure in other processes involving cytoskeletal rearrangements.","language":"en"},{"key":"dc.format.extent","value":"3469852 bytes","language":null},{"key":"dc.format.mimetype","value":"application\/pdf","language":null},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":null},{"key":"dc.rights","value":"Attribution-NonCommercial-NoDerivatives 4.0 International","language":null},{"key":"dc.rights.uri","value":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/","language":null},{"key":"dc.title","value":"The roles of the IG-alpha and IG-beta cytoplasmic domains in B cell antigen receptor (BCR) internalization and trafficking","language":"en"},{"key":"dc.type","value":"Text","language":null},{"key":"dc.degree.name","value":"Master of Science - MSc","language":"en"},{"key":"dc.degree.discipline","value":"Zoology","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":null},{"key":"dc.date.graduation","value":"2009-05","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Science, Faculty of","language":null},{"key":"dc.description.affiliation","value":"Zoology, Department of","language":null},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]