Molecular mechanisms that control expression of the B lymphocyte antigen receptor complex.
The B cell receptor for antigen (BCR) is a complex of membrane immunoglobulin (mIg) and at least two other proteins, Ig alpha (mb-1) and Ig beta (B29). This complex promotes surface expression of the BCR and acts to transduce an activation signal. We have used a system of mu heavy chain constructs transfected into murine B cell lines to probe structure-function relationships in the BCR complex. One mutant mu chain, in which two polar transmembrane residues (Tyr587, Ser588) are replaced with valine, fails to associate with Ig alpha and Ig beta and is incapable of transducing signals as a result of mIg cross-linking. This mutant is expressed on the surface at high levels when transfected into a plasmacytoma line that lacks Ig alpha, whereas wild-type mu is retained in this cell line in the endoplasmic reticulum. Pulse-chase and immunoprecipitation analyses indicate that the mutant is more rapidly released from calnexin than the wild-type mu. Further, transfection of Ig alpha into this Ig alpha-negative cell line allows release of the mu chain from calnexin and surface expression of the BCR. These results identify the transmembrane residues of mu heavy chain that control binding to calnexin and Ig alpha, and suggest that calnexin-dependent intracellular retention is an important control mechanism for expression of the BCR complex.
Grupp
S A
SA
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Mitchell
R N
RN
Schreiber
K L
KL
McKean
D J
DJ
Abbas
A K
AK
D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000378:metabolism*; D001692:Biological Transport; D051925:CD79 Antigens; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D037281:Calnexin; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; D002135:Calcium-Binding Proteins; C497882:Cd79a protein, mouse; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D037281:Calnexin; D002118:Calcium