Selective proteolysis of the J chain component in human polymeric immunoglobulin.
To clarify the losses that have been observed in the J chain portion of human IgM and IgA, were carried out studies on the enzymatic susceptibility of the J polypeptide. When Waldenström macroglobulins and myeloma IgA polymers were subjected to limited proteolysis with various endopeptidases, only subtilisin was found to attack the J chain component. The pattern of cleavage was a function of the polymer species. The J chain in IgM was highly susceptible to digestion, quantitative cleavage being achieved at very low enzyme to IgM ratios and without significant changes in the remaining pentamer structure. Analyses of the digestion products showed that the initial cleavage occurred at an exposed region midway in the J sequence and was followed by extensive degradation of the carboxy-terminal segment. These findings indicated that the observed loss of the IgM J component can be explained by the inadvertent introduction of subtilisin in vitro or by the attack of in vivo enzymes with a specificity similar to subtilisin. In contrast, the IgA  J chain was found to be much more resistant to subtilisin proteolysis; its cleavage required higher enzyme concentrations and was accompanied by significant degradation of the alpha-chains. Thus, it appears unlikely that the IgA J polypeptide is degraded by either in vitro or in vivo enzymes unless its accessibility is first enhanced by changes in the IgA Fc structure.
D000595:Amino Acid Sequence; D002918:Chymotrypsin; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes; D006801:Humans; D005779:Immunodiffusion; D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D008259:Macroglobulins; D009194:Myeloma Proteins; D013381:Subtilisins; D014357:Trypsin; D014461:Ultracentrifugation
D000939:Epitopes; D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D008259:Macroglobulins; D009194:Myeloma Proteins; D013381:Subtilisins; D002918:Chymotrypsin; D014357:Trypsin