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Interactions between the extracellular and transmembrane domains of IG-alpha/beta heterodimer are required for BCR assembly and cell surface expression

University of British Columbia

The B cell antigen receptor (BCR) is expressed on the surface of B-lymphocytes where it binds antigen and transmits signals that regulate B cell activation, growth and differentiation. The BCR is composed of membrane IgM (mlgM) and two signaling proteins, Ig-α and Ig-β. If either of the signaling proteins is not expressed, the incomplete mlgM-containing BCR will not traffic to the cell surface. Our hypothesis is that specific protein:protein interactions between both the extracellular and transmembrane (TM) regions of Ig-α and Ig-β are necessary for receptor assembly, cell surface expression and effective signaling to support the proper development of B cells. While previous work has shown the importance of the T M region in BCR assembly, this study indicates that a heterodimer of the extracellular domains of Ig-α and Ig-β are also required for proper association with mlgM. Cell lines expressing mutated Ig-α proteins that did not heterodimerize with Ig-β in the extracellular and T M domains were unable to properly assemble the BCR. Conversely, an Ig-α mutant with an Ig-β cytoplasmic tail (Cβ (α/α/β)) was able to assemble with the rest of the BCR and traffic to the cell surface. Thus, both the extracellular and TM regions if the Ig-α/Ig-β must be properly associated in order for the BCR to assemble. Additionally, an Ig-α mutant with a truncated cytoplasmic domain (ΔαKVK (α/α/0)) was not able to associate with Ig-β, indicating that the cytoplasmic domain may play a role in BCR assembly. Further studies with truncation mutants are required to confirm this result. In the future additional Ig-α/Ig-β mutants will be expressed to better define the regions of protein:protein interactions.

Text

2010-01-05

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http://hdl.handle.net/2429/17518

Zoology

University of British Columbia

UBCV

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