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 subclass of human gamma-A-globulins (gamma-A2) which lacks the disulfied bonds linking heavy and light chains.

The gammaA2-subgroup of gammaA-globulins, previously delineated by antigenic studies, was found to differ strikingly from other immunoglobulins in the manner in which the polypeptide chains are bound together. The heavy and light chains were not linked to each other by disulfide bonds. Instead the light chains were disulfide linked to one another, and were present in the gammaA2-molecule as disulfide bridged L-L dimers.

Catabolism of human gammaG-immunoglobulins of different heavy chain subclasses. I. Catabolism of gammaG-myeloma proteins in man.

The rates of catabolism of human gammaG-immunoglobulins of subclasses gammaG(1), gammaG(2), gammaG(3), and gammaG(4) were studied by determining the rates of elimination from the circulation of pairs of (131)I-and (125)I-labeled gammaG-myeloma proteins in 57 patients suffering from cancer other than multiple myeloma. On the average, gammaG(1)-, gammaG(2)-, and gammaG(4)-myeloma proteins were catabolized at a rate similar to that of normal gammaG-immunoglobulin, whereas gammaG(3)-myeloma proteins were catabolized more rapidly than normal gammaG-immunoglobulin. The average half-lives for the myeloma proteins were 12.

Human monoclonal gamma G-cryoglobulins with anti-gamma-globulin activity.

Seven human gammaG-myeloma proteins which were also cryoglobulins were studied with respect to their reactivity with gammaG-globulins as well as with regard to their antigenic classification within the gammaG-heavy chain subclasses. Five of the seven cryoglobulins studied were positive in at least two of the three tests used to assay for anti-gamma-globulin activity. One protein was only weakly positive in one test system and another was negative in all test systems.

A case of tetramer Bence Jones proteinaemia.

A case of Bence Jones proteinaemia without concomitant Bence Jones proteinuria is described. The protein consisted of four λ type light chains with a molecular weight of 84,000. A pair of dimers were non-covalently bonded to form the tetramer.

Carboxy-terminal amino acids of gamma-A and gamma-M heavy chains.

The carboxy-terminal amino acids of alpha-and micro-chains from human immunoglobulins and alpha-chains from mouse immunoglobulins have been determined by carboxypeptidase digestion and hydrazinolysis. The data suggest the following carboxy-terminal sequences: human micro: Ala-Gly-Thr-Cys-TyrCOOH; human alpha: Thr-Cys-TyrCOOH; murine alpha: (Ileu, Cys)-TyrCOOH.

Recombination of heavy and light chains of human gamma-a-myeloma proteins: formation of hybrid molecules and configurational specificity.

The present studies demonstrate that the conditions necessary for reductive cleavage, isolation, and recombination of L and H polypeptide chains of human gammaA-myeloma globulins parallel those required for similar manipulation of the component chains of gammaG-globulin. Specificity of recombination was shown for chains derived from the same protein. In contrast, no intradass preferential recombination was demonstrable.

Low-molecular-weight proteins related to Bence Jones proteins in multiple myeloma.

Urinary proteins distinct from Bence Jones proteins, but sharing antigenic determinants, were found in the urine of a number of patients with multiple myeloma. These components were smaller in size and antigenically deficient compared with Bence Jones proteins. They were best detected with antiserums to the homologous Bence Jones proteins and, in some cases, were related to the variable portion of the Bence Jones protein molecule.

Specificity of recombination of H and L chains from human gamma-G-myeloma proteins.

Dissociated H and L chains of human gammaG-myeloma proteins were recombined by removal of conditions interrupting non-covalent interactions. In the process of recombination 7S molecules were formed. It was demonstrated that the H chains from individual gammaG-myeloma proteins recombine with their own L chains but also with L chains derived from other myeloma proteins.

INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS.

The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled gamma-globulin and for the localization of these determinants on the gamma-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of gamma-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum.

H CHAIN SUBGROUPS OF MYELOMA PROTEINS AND NORMAL 7S GAMMA-GLOBULIN.

Through the use of a variety of antisera to isolated myeloma proteins, four subgroups of 7S gamma-globulin type proteins were readily distinguished. The first, the Vi subgroup, consisted of ten of 64 myeloma proteins studied. The second, the We group, contained the majority of myeloma proteins.