Human myeloma IgG half-molecules. Catabolism and biological properties.
A human IgG1 myeloma protein that has a delection in the third constant domain of the heavy chain (Cgamma3) and forms two-chain half-molecules was studied for its in vivo turnover and its ability to fix C1q and hemolytic complement, to bind to human lymphocytes, neutrophils, and monocytes, and to induce a passive cutaneous reaction in guinea pigs. In both man and monkeys, the half-molecule was rapidly catabolized and in part excreted into the urine. The half-life in man was 4.3 days and the fractional turnover 165% per day; 7.6% of the intravascular pool was excreted into the urine per day. Although the 7S four-chain myeloma protein could not be obtained in a pure form, the elimination from the serum of a partially purified preparation suggested that it was also rapidly catabolized. The unaggregated half-molecule neither formed complexes with C1q, cound to human lymphocytes, neutrophils, and monocytes, nor elicited a reverse passive cutaneous reaction in guinea pigs. In contrast, the aggregated half-molecule fixed hemolytic complement and bound to the human white cells similarly to an intact IgG1 myeloma protein. In order to explain the biological activities of this half-moleculr, it is postulated that IgG1 may have several (at least two) submolecular sites for a given biological activity that are localized on both the Cgamma2 and Cgamma3 domains. Proteins having both sites would be capable of binding to C1q and Fc cell receptors in unaggregated in order to obtain half-molecule, must be aggregated in order to obtain this binding.
D000818:Animals; D003168:Complement Fixation Tests; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D008251:Macaca; D008297:Male; D008407:Mast Cells / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis; D011485:Protein Binding
D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G