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.
Cell Biology Group, Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Janis
J
Dylke
Jared
J
Lopes
May
M
Dang-Lawson
Steve
S
Machtaler
Linda
L
Matsuuchi
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