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UBC Theses and Dissertations

The roles of the IG-alpha and IG-beta cytoplasmic domains in B cell antigen receptor (BCR) internalization and trafficking Jang, Caren Lynn


The B cell antigen receptor (BCR) is expressed on the surface of B lymphocytes where it can bind antigen then transmit signals which regulate activation, growth, and differentiation. These signals can induce a number of cytoskeletal rearrangements leading to changes in adherence, spreading, polarity, immune synapse formation, migration and internalization. In the latter situation, BCR internalization results in the uptake of antigen which can then be processed and presented to T cells on MHC II. The relative importance of regions within the Igα and Igβ cytoplasmic domains have been studied in terms of signaling but their roles in BCR internalization and trafficking are less clear. We hypothesize that the structure of Igα and Igβ cytoplasmic domains is important for normal BCR internalization and trafficking. An Igα and Igβ deficient lymphoid cell line has been used to express mIgM along with a panel of Igα and Igβ mutants in order to compare their internalization and subcellular localization in both a qualitative and quantitative manner. Using this system it was shown that the Igα and Igβ cytoplasmic domains are each sufficient for internalization and that the internalization signal is contained in a region past the first tyrosine residue on either chain, Y176 and Y195 respectively. It was also determined that the Igα cytoplasmic domain makes a larger contribution to internalization than the Igβ tail and that a 4 amino acid motif normally contained within the Igα ITAM is sufficient to allow internalization. In terms of receptor trafficking it was shown that each cytoplasmic domain is sufficient for trafficking to lysosomal compartments but that a normal rate of trafficking likely requires the tandem effects of both Igα and Igβ. It was also shown that BCR-induced signaling is generally reduced in mutants with an Igα truncation or an Igβ duplication, but that the Igα truncation results in an increased and sustained level of ERK phosphorylation. Further studies with the panel of mutants will determine the role of Igα and Igβ structure in other processes involving cytoskeletal rearrangements.

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