Synthesis and Assembly of Immunoglobulins by Malignant Human Plasmacytes

Abstract

The basic features of "y-globulin synthesis and assembly have been elucidated in hyperimmune rabbit lymph nodes and malignant tissues of the mouse (1-12). These studies indicate that heavy (H) and light (L) chains are synthesized independently on ribosomes of different sizes (3, 4) and that L chains are then released from their ribosomes into an intracellular pool (5). No equivalent pool of soluble (released) intracellular H chains has been demonstrated (6). In at least four mouse tumors, L chains combine with nascent H chains on polyribosomes before their release (3, 6, 7). The assembly of "y-globulin occurs intracellularly (8, 9), and there is a 20 to 30 minute lag between the synthesis of chains and their secretion (9). During this period, the attachment of the major part of the carbohydrate moieties takes place (11).The relative amounts of H and L chains synthesized and the patterns of assembly differ in several of the immunoglobulin synthesizing tissues studied to date. Some malignant and hyperimmune cells appear to be balanced with respect to the number of L and H chains secreted while others secrete excess free light chains. There is also evidence that the H-L dimer serves as an intermediate in the assembly of "y-globulin by some mouse plasmacytomas while others are assembled primarily through an H-H dinaer (6, 9, 12). G a m m a globulin synthesis by malignant tissues from humans with multiple myeloma has been examined (13, 14) but a systematic study of this process in various types of human plasma cell tumors has not yet been performed. The

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).…”

Unfolded protein response activation reduces secretion and extracellular aggregation of amyloidogenic immunoglobulin light chain

“…Plasma cells normally secrete LC as IgGs [assemblies of two LCs and two heavy chains (HCs)], or as free LCs. However, in AL patients, LCs are predominantly secreted independent of HCs, sometimes as monomers, but generally as disulfide-linked homodimers called Bence−Jones proteins-the common precursor for LC aggregation (22,23). Furthermore, LC ER quality Significance Light-chain amyloidosis (AL) is a devastating human disease involving the clonal expansion of a plasma cell and the secretion of destabilized, amyloidogenic immunoglobulin light chains (LCs).…”

Ein Plasmozytomfall mit immunhistochemisch verschiedenen Zellpopulationen und seine Bedeutung f�r die immunhistochemische Monoclonalit�tsbestimmung von Lymphomzellen

“…Possible repressions or derepressions of some of the respective genes during the course of the disease might result in production of different amounts of heavy and light chains. At least, it is well known that myelomas do not form normal proportions of heavy and light chains (Zolla et al 1970;Baumal and Scharff 1973). Usually light chains predominate, and in about 20% of plasmocytoma cases solely light chains are found (Williams et al 1966;Hobbs 1974).…”