ASSEMBLY AND INTRACELLULAR-TRANSPORT OF THE HUMAN B-CELL ANTIGEN RECEPTOR COMPLEX

The B cell antigen receptor (BCR) complex consists of transmembrane (m ) lg, in non-covalent association with a disulphide-linked heterodimer of mb-1 and B29 gene products, The MB-1-B29 heterodimer is required f or deposition of the BCR at the plasma membrane, as well as for coupli ng of the antigen receptor to intracellular signal transduction cascad es, We have performed biosynthetic labelling studies using the mature B cell line Ramos to investigate the process of assembly of the BCR co mponents; We conclude that association of the four components, Ig-heav y chain (HC) and -light chain (LC), MB-1 and B29, is required and suff icient to permit exit of the BCR complex out of the endoplasmic reticu lum (ER), With the short pulse labelling procedures used, no evidence was found for transient participation of other molecules in complex fo rmation, A 32 kDa glycoprotein was identified, which is serologically related to MB-1, but has a more acidic isoelectric point (pl) and a pr otein backbone of 21 kDa, as compared with 25 kDa for MB-1, This prote in did not appear to participate in BCR complex formation and is most likely degraded prior to reaching the cis-Golgi, The MB-1 component wa s found to be the rate-limiting step in BCR complex formation, while I g-HC, -LC and B29 are synthesized in excess. Ig-HC and -LC form disulp hide-linked tetrameric complexes within 3 min after biosynthesis, with which B29 and MB-1 components associate independently, followed by di sulphide bond formation between these heterodimeric partners: While pa rtial BCR complexes containing B29 and mlg-H(2)L(2) tetramers are rapi dly 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.