Synthesis and Assembly of Immunoglobulins by Malignant Human Plasmacytes and Lymphocytes

Abstract

Bone marrow or lymph node cells from 10 patients whose sera contained large amounts of monoclonal IgM proteins were incubated with radioactive amino acids in short-term tissue culture. Samples of soluble cytoplasmic extracts and secreted material were examined by immunologic precipitation with specific antisera, acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and sucrose gradient centrifugation. In all samples studied, 8S IgM was the major intracellular precursor of the fully assembled 19S protein. Cells obtained from some patients contained little or no fully assembled 19S protein intracellularly; however, cells from most patients seemed to accumulate fully assembled 19S molecules intracellularly before secretion. Secreted material from both groups contained large amounts of 19S IgM. The differentiation between accumulating and nonaccumulating cells did not correlate with heavy or light chain antigenic type. Synthesis and assembly appeared to be identical in cells obtained from different anatomic sites in the same patient Studies carried out in one patient before and after therapy revealed no qualitative differences in the pathway of assembly and reflected only a decrease in the total number of immunoglobulin-producing cells.

Monomeric (7S) IgM found in the serum of rheumatoid arthritis patients share idiotypes with pentameric (19S) monoclonal rheumatoid factors.

“…The remaining "background," RCRI+ plasma cells may represent immunoglobulin molecules produced by a set of separate non-RF related B-cell clones that share some determinants with the 7S, IgM obtained from an RF-"RA" patient (Ho), and reduced and alkylated normal polyclonal IgM, both failed to absorb any activity of specific anti-RCRI antibodies (Table II). These observations in conjunction with those seen in hemagglutination inhibition assay (Tables IV and V) Finally, 7S, IgM appear to be independent biosynthetic IgM molecules and not degradation products of pentameric IgM (3,5,14,26). Except for its low molecular weight as compared to the pentamer, and the difference in binding avidity for the Fc portion ofIgG, 7S, IgM molecules are similar to their 19S counterparts (3-6, 13).…”

Cellular localization of rheumatoid factor idiotypes.

“…1) (19,20,21). In human 19 S IgM secreting tumors, the proportion of intracellular pentamer varied in different cases (22), but no data are available on PWM-stimulated cells that may be relatively immature plasma cells. It is known that these cells express Ia determinants and surface immunoglobulins that are absent from mature plasma cells (23).…”

Synthesis, Assembly, and Secretion of Gamma Globulin by Mouse Myeloma Cells

“…Although assembly of the immunoglobulin molecule has not been studied as extensively in other species, HL has been shown to be a precursor in one human IgG myeloma (33), in a number of IgM macroglobulinemias (34), and in normal rabbit IgG (29). Continuous human lymphoid cell lines secreting human IgG use H2 and HzL as major intermediates (35).…”