Role of the extracellular and transmembrane domain of Ig-alpha/beta 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-alpha and Ig-beta. 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-alpha and Ig-beta 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-alpha and Ig-beta are also required for proper association with mIgM. Cell lines expressing mutated Ig-alpha proteins that did not heterodimerize with Ig-beta in the extracellular and TM domains were unable to properly assemble the BCR. Conversely, an Ig-alpha mutant with an Ig-beta cytoplasmic tail (Cbeta (alpha/alpha/beta)) was able to assemble with the rest of the BCR, in particular with Ig-beta, and traffic to the cell surface. Thus, both the extracellular and TM regions of the Ig-alpha/Ig-beta must be properly associated in order for the BCR to assemble.
Dylke
Janis
J
Cell Biology Group, Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Lopes
Jared
J
Dang-Lawson
May
M
Machtaler
Steve
S
Matsuuchi
Linda
L
D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D051925:CD79 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D000906:Antibodies; D051925:CD79 Antigens; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins