Proteolytic degradation of IgD and its relation to molecular conformation.

“Spontaneous” degradation of IgD into Fc and Fab fragments frequently occurs during purification and storage. Because proteolysis is the likely mechanism for cleavage of IgD under these conditions, the susceptibility of IgD and other immunoglobulins to digestion with trypsin, plasmin, and papain was analyzed. IgD was much more susceptible to proteolysis than the other immunoglobulins studied. The fast fragments, Fc, obtained after spontaneous degradation and after proteolysis were immunologically identical and this was also true of the slow fragments, Fab. The sedimentation coefficients and Stokes radii of the intact protein and fragments were determined and the frictional coefficient ratios and molecular weights calculated. Both the intact IgD and the Fc fragment appear to be less compact than other intact immunoglobulins or the Fc fragment of IgG. We propose that this apparent difference in conformation may account in part for the increased susceptibility of IgD to proteolysis. Finally, attention is drawn to the potential contamination of IgD preparations with the fifth component of complement (C5).