Plasma cell tumour-formation and antigen-binding myeloma proteins in mice.

Abstract

Plasmacytoma can be induced in the inbred BALB/c mouse by the injection of mineral oil or implants of solid plastics. This induction depends on three factors: firstly, an abnormal peritoneal granulomatous tissue; secondly, genetically determined factors in the strain BALB/c genotype; and, thirdly, the presence of a gastrointestinal and respiratory microbial flora. The incidence of plasmacytomas following three injections of mineral oils or purified isoparaffins ranges from 40 to 600'. The tumours develop in the peritoneal oil granuloma and often remain localized in the peritoneal connective tissues. In several series of myeloma proteins in this strain of mice the IgA class predominates; 60-66%/' of all tumours that produce a detectable heavy chain class myeloma protein produce an IgA class protein. This finding strongly implies that a portion of the total immunocyte population is more prone to neoplastic transformation. Because IgA myeloma proteins in BALB/c mice are usually polymeric molecules, these proteins can be tested for their ability to bind polyvalent antigens by precipitin reactions. Using this method myeloma proteins with antigenbinding activity have been found to several different antigens. The chemical determinants have been identified for many and include: nitrophenyl compounds, al --3 dextrose (nigerotriose), methyl a-D-galactoside, methyl f3-D-galactoside (probably more specifically to p 1 -6 linked galactose), N-acetyl glucosamine in P1-+3 linkages, N-acetyl D-mannosamine, phosphoryl choline, choline, and a trypsin-sensitive determinant common to antigenic substances produced by salmonella. Other myeloma proteins have been found to precipitate with antigens of bacterial origin. The chemical determinants for these have not yet been established. The actual incidence of active M-components in a series of tumours ranges from 5 to 10% when test antigens containing the determinants mentioned above are used. Many of the antigens can be shown to be produced by organisms in the gastrointestinal and respiratory microbial flora. The chemical determinants, however, to which the myeloma proteins are directed may be found in some cases on autogenous macromolecules. Nevertheless, bacterial antigens containing these determinants are probably highly immunogenic and the precursors of the tumour cells were probably responding to these antigens before neoplastic transformation. The finding of several plasmacytomas of independent origin that produce myeloma proteins which identify the same antigen or chemical antigenic determinant supports this suggestion.