A role for human heavy chain binding protein in the developmental regulation of immunoglobin transport.
Human EBV transformed lymphoblastoid cell lines and lymphomas representing various stages of B cell development were examined for heavy chain binding protein (BiP) expression and its association with immunoglobin (Ig) heavy chains. Human BiP was shown to migrate with an apparent mol. wt of 79,000 and to have a pI of approximately 5.5 in all the human cell lines examined. Both the mum and the mus heavy chains synthesized in a pre-B cell line (mu+, LC-) remained associated with BiP and were all found to be endo H sensitive, suggesting that this association occurred in the endoplasmic reticulum (ER). Surface Ig+ B cell lines produce membrane type heavy chains which are expressed on the cell surface and secretory type heavy chains which remain intracellular. The membrane type mu heavy chains produced by a surface Ig+ B cell line were not associated with BiP after assembling with light chains and processing in the Golgi. However, the secretory type mu heavy chains synthesized by these same cells did not combine efficiently with LC and a significant quantity remained associated with BiP and were not secreted suggesting that BiP is involved in the divergent transport of membrane and secretory mu heavy chains in surface Ig+ B cell lines. In Ig secreting plasmacytoid lines the heavy chains were only associated with BiP prior to assembling with LC. When LC assembly was inhibited, the association of heavy chains with BiP was prolonged and Ig secretion was blocked. Therefore, BiP was found to participate in the post-translational processing of mu heavy chains synthesized by human lymphoid cell lines representing all stages of B cell development. Further, heavy chains that remained associated with BiP were not transported to the cell surface or secreted while heavy chains that were only transiently associated with BiP chains were expressed on the cell surface or secreted.
D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000502:physiology*; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000502:physiology*; D007525:Isoelectric Focusing; D018832:Molecular Chaperones; D014415:Tunicamycin / Q000494:pharmacology
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D018832:Molecular Chaperones; D014415:Tunicamycin