Myeloma polypeptide chain

Although the RNA transformation experiments are often considered to be arguments against the precommitment hypothesis, I believe that in fact they are irrelevant to the subject. First of all, it is not surprising that a cell equipped with a functional protein synthetic machinery would be able to translate RNA to protein if the former could enter the cell intact. It has recently been shown that RNA, injected into amphibian eggs, will be readily translated into myeloma polypeptide chain (Stevens and Williamson, 1972). I suggest the RNA transformation experiments should be disregarded in the present context as they probably do not reflect normal in vivo processes. 

The antibodies are similar in structure to other globulin proteins which are present in serum of vertebrates [9], The antibody molecule consists of two light polypeptide chains and two heavy polypeptide chains [10]. The amino acids are present in all the chains but the number of residues and the sequence will vary in different antibody multiforms [9], Light chains contain approximately 220 amino add residues and heavy chains about 450 residues. The complete sequence of the chains of human IgG myeloma protein has been determined by Edelman [11], The chains are held together in the unique conformational structure of the antibody molecule by a few covalent disulfide bonds between the chains and many electrostatic bonds between the amino groups of one chain and the hydroxyl groups of another chain. The covalent bonds are represented in Formula 1, 2 and 3 [peptide, disulfide and... 

This work was extended by the important investigations of Weigert et al. (56,57) who investigated the amino acid sequences of the variable portions of twelve different X chains. All the tryptic peptides were aligned and their amino acid compositions determined. A comparison with the sequence reported by Appella permitted the ordering of amino acids. The polypeptide chains sequenced included X chains isolated from IgA myeloma proteins, as well as urinary Bence Jones proteins from mice with serum myeloma proteins of the IgA, IgM, and IgG2a classes. Two of the proteins were obtained from the transplantable tumors that were used by Appella and Perham. 

We will use the phrase autologous chains to denote H and L chains derived from a given population of antibody molecules (not necessarily homogeneous) or from one myeloma protein. The question at issue is whether autologous chains recombine preferentially in a competitive situation in which a polypeptide chain from another antibody or myeloma protein is also present. 

Idiotypic specificities on free L chains have been localized to the variable half of the polypeptide chain by Tan and Epstein, who isolated such fragments from the urine of a patient with multiple myeloma (92). The corresponding, intact Bence Jones protein was also purified and used to prepare antibodies in rabbits which, after appropriate absorption, reacted with idiotypic determinants of the immunogen. A line of identity was obtained in the reaction of these anti-D antibodies with the Bence Jones protein and the fragment comprising the variable region. Thus, all the individually specific determinants appeared to be represented in the variable segment. 

Rose, S.M., Kuehl, W.M., Smith, G.P. (1977). Cloned MPC 11 myeloma cells express two kappa genes a gene for a complete light chain and a gene for a constant region polypeptide. Cell 12, 453-462. 

The specificity of protein transport necessitates a method for the cell to distinguish cytoplasmic from secretory proteins. In two studies of in vitro translation of mRNA from myeloma cells, Milstein et al. (1972) and Swan et al. (1972) found that the immunoglobulin light chain is synthesized as a precursor 3000 Da larger than the mature protein. They also found that the extra material is a polypeptide extension at the amino terminus of the mature protein product, and is cleaved by a protease activity found in ER membrane. Schechter et al. (1975) later determined the amino acid sequence of this amino-terminal addition. These results implied that the information necessary to specify secretion is contained in the extra material. 

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