Role of the extracellular and transmembrane domain of Ig-α/β in assembly of the B cell antigen receptor (BCR)

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 (mIgM) and two signaling proteins, Ig-α and Ig-β. If either of the signaling proteins is not expressed, the incomplete mIgM-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 TM 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 mIgM. Cell lines expressing mutated Ig-α proteins that did not heterodimerize with Ig-β in the extracellular and TM 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, in particular with Ig-β, and traffic to the cell surface. Thus, both the extracellular and TM regions of the Ig-α/Ig-β must be properly associated in order for the BCR to assemble.