Assembly and intracellular transport of the human B cell antigen receptor complex.
The B cell antigen receptor (BCR) complex consists of transmembrane (m) Ig, in non-covalent association with a disulphide-linked heterodimer of mb-1 and B29 gene products. The MB-1-B29 heterodimer is required for deposition of the BCR at the plasma membrane, as well as for coupling of the antigen receptor to intracellular signal transduction cascades. We have performed biosynthetic labelling studies using the mature B cell line Ramos to investigate the process of assembly of the BCR components. We conclude that association of the four components, Ig-heavy chain (HC) and -light chain (LC), MB-1 and B29, is required and sufficient to permit exit of the BCR complex out of the endoplasmic reticulum (ER). With the short pulse labelling procedures used, no evidence was found for transient participation of other molecules in complex formation. A 32 kDa glycoprotein was identified, which is serologically related to MB-1, but has a more acidic isoelectric point (pl) and a protein backbone of 21 kDa, as compared with 25 kDa for MB-1. This protein did not appear to participate in BCR complex formation and is most likely degraded prior to reaching the cis-Golgi. The MB-1 component was found to be the rate-limiting step in BCR complex formation, while Ig-HC, -LC and B29 are synthesized in excess. Ig-HC and -LC form disulphide-linked tetrameric complexes within 3 min after biosynthesis, with which B29 and MB-1 components associate independently, followed by disulphide bond formation between these heterodimeric partners. While partial BCR complexes containing B29 and mlg-H2L2 tetramers are rapidly formed and have a half-life of a few hours in the ER, entry of MB-1 into these complexes controls exit out of this compartment.
Brouns
G S
GS
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
de Vries
E
E
Borst
J
J
D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001692:Biological Transport; D002051:Burkitt Lymphoma / Q000473:pathology; D051925:CD79 Antigens; D003553:Cystine / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism*; D007148:Immunoglobulin mu-Chains / Q000378:metabolism*; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell; D003553:Cystine