Absence of disulfide bonds linking the heavy and light chains: a property of a genetic variant of gamma-A2 globulins.

The gammaA2 globulins have attracted considerable interest because of the absence of the disulfide bonds linking the heavy and light chains characteristic of all other human immune globulins. Recently a genetic marker (Am(2)) has been found which delineates two genetic variants of gammaA2 globulins that are controlled by allelic genes. These differ markedly in incidence in different populations with a marked preponderance in Caucasians of the type possessing the Am(2) marker. A study of 22 gammaA2 myeloma proteins primarily from Caucasians showed that 20 were Am(2)(+), and 2 were Am(2)(-). All of the positive type dissociated in the presence of acid or urea into heavy and light chain dimers without reduction of disulfide bonds, as expected from the earlier studies. However, the two Am(2)(-) proteins failed to dissociate in the presence of acid, urea, guanidine, or detergent. It was only after partial reduction and alkylation that these molecules split into heavy and light chains. Thus the unique absence of disulfide bonds linking the heavy and light chains is a property of only one genetic variant and not of all gammaA2 proteins.