Distinct intracellular fates of membrane and secretory immunoglobulin heavy chains in a pre-B cell line.
The intracellular fates of membrane and secretory immunoglobulin heavy chains were examined in a pre-B cell line that has switched to the gamma isotype. The membrane form of the heavy chain (gamma m) was rapidly degraded while the secretory form (gamma s) was retained intracellularly in association with BiP. The degradation of gamma m could not be inhibited by ammonium chloride, chloroquine, or monensin suggesting that it occurred in a nonlysosomal compartment. The inability to detect any Endo H-resistant form of gamma m before its degradation suggested that degradation occurs before entry into the Golgi compartment. Degradation of gamma m could be inhibited by incubation at 24 degrees C. In a derivative of this cell line expressing a transfected kappa gene, gamma s formed disulfide linked tetramers with kappa and was secreted, while gamma m, although associated with kappa, continued to be rapidly degraded. These observations suggest that membrane and secretory heavy chain proteins are retained by distinct intracellular mechanisms. Although masking of the CH1 domain abrogates gamma s retention, this domain does not influence the intracellular fate of gamma m.
Molecular Immunology Laboratory, Cancer Center of Massachusetts General Hospital, Boston.
A K
AK
Bachhawat
S
S
Pillai
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D020126:Brefeldin A; D002461:Cell Line, Transformed; D002738:Chloroquine / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
D003517:Cyclopentanes; D007071:Immunoglobulin A, Secretory; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D011947:Receptors, Antigen, B-Cell; D000643:Ammonium Chloride; D020126:Brefeldin A; D002738:Chloroquine; D008985:Monensin