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Association of the B cell antigen receptor with protein chaperones

University of British Columbia

The multimeric B cell antigen receptor (BCR) consists of four different receptor subunits: immunoglobulin heavy chain (Igu), light chain (X), Iga and Igp. These four chains must assemble correctly in the endoplasmic reticulum (ER) before the receptor can be transported to the cell surface. Recent evidence in lymphoid cells suggests that during receptor assembly the mlgM part (Igu. + light chain) of the BCR interacts with chaperone proteins in the ER. In this study we have examined the proteimprotein interactions between three chaperones, GRP78 (BiP), GRP94 and calnexin with the wildtype BCR and with a BCR containing an altered u heavy chain. By generating cell lines that express various intermediate assembled forms of the BCR (Igu+A,+Iga+Ig(3, Igu+Ji+Iga, Igu+k, Igu, X, Iga, or Igp), we have been able to identify the protein chaperones associated with each receptor subunit. Our data showed that, when expressed by itself in non-lymphoid cells, Iga associated with GRP94 and that the level of association increased dramatically when other BCR chains were co-expressed. Iga was found associated with BiP and calnexin in lymphoid cells, however we believe these interactions were likely mediated through other BCR chains present. We could find no evidence of Igp interactions with any of the other chaperone proteins tested. Interestingly, our results also showed that, when expressed alone, X light chain associated with calnexin. Consistent with the literature, u heavy chain was found associated with all three protein chaperones tested. Our results are consistent with the model suggesting an ordered and sequential interaction between assembling BCR components and the GRP78 and GRP94 protein chaperones during early stages during receptor assembly. Recent evidence suggesting the membrane spanning region of Igu is particularly important for interacting with protein chaperones led us to examine an altered form of u heavy chain that escapes ER retention in lymphoid cells. We found that this mutant did not escape ER retention in non-lymphoid cells nor did it bind chaperones differently from wildtype. This observations suggests that the presence of B cell specific proteins may mediate the transport of the mutant protein to the cell surface in lymphoid cells.

Thesis/Dissertation

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2009-03-25

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http://hdl.handle.net/2429/6481

Zoology

University of British Columbia

UBCV

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