Association of B lymphocyte antigen receptor polypeptides with multiple chaperone proteins

Abstract

The B cell antigen receptor (BCR) is comprised of four different polypeptides, immunoglobulin (Ig) heavy chain, Ig light chain, and the two signaling subunits of this receptor, Ig-α and Ig-β. These four chains must assemble correctly in the endoplasmic reticulum (ER) before the BCR can be transported to the cell surface. The roles of the different chaperone proteins in mediating the assembly of mIg with the Ig-α/β are not fully understood. To gain insights into the roles of chaperone proteins in BCR assembly, we have generated transfected non-lymphoid cell lines that express various intermediate assembled forms of the BCR and used them to examine the interactions of chaperone proteins with subunits of the BCR. We examined the interactions of BiP (GRP78), GRP94 and calnexin with the μ heavy chain, λ light chain, Ig-α and Ig-β. We report for the first time that Ig-α associates with GRP94 and that this interaction increases dramatically when other BCR chains are co-expressed. In contrast, the μ heavy chain interacts strongly with BiP (GRP78) when expressed by itself but this interaction is reduced when the λ light chain is expressed, with the resulting μλ complexes interacting with GRP94 and calnexin. Thus, our data are consistent with the idea that there is an ordered association of BCR components with different protein chaperones during BCR assembly.