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The plasma cell disorders are monoclonal neoplasms related to each other by virtue of their development from common progenitors in the B lymphocyte lineage. Multiple myeloma, Waldenström's macroglobulinemia, primary amyloidosis (Chap. 112), and the heavy chain diseases comprise this group and may be designated by a variety of synonyms such as monoclonal gammopathies, paraproteinemias, plasma cell dyscrasias, and dysproteinemias. Mature B lymphocytes destined to produce IgG bear surface immunoglobulin molecules of both M and G heavy chain isotypes with both isotypes having identical idiotypes (variable regions). Under normal circumstances, maturation to antibody-secreting plasma cells and their proliferation is stimulated by exposure to the antigen for which the surface immunoglobulin is specific; however, in the plasma cell disorders the control over this process is lost. The clinical manifestations of all the plasma cell disorders relate to the expansion of the neoplastic cells, to the secretion of cell products (immunoglobulin molecules or subunits, lymphokines), and to some extent to the host's response to the tumor. Normal development of B lymphocytes is discussed in Chap. 314.


There are three categories of structural variation among immunoglobulin molecules that form antigenic determinants, and these are used to classify immunoglobulins (Chap. 314). Isotypes are those determinants that distinguish among the main classes of antibodies of a given species and are the same in all normal individuals of that species. Therefore, isotypic determinants are, by definition, recognized by antibodies from a distinct species (heterologous sera) but not by antibodies from the same species (homologous sera). There are five heavy chain isotypes (M, G, A, D, E) and two light chain isotypes (κ, λ). Allotypes are distinct determinants that reflect regular small differences between individuals of the same species in the amino acid sequences of otherwise similar immunoglobulins. These differences are determined by allelic genes; by definition, they are detected by antibodies made in the same species. Idiotypes are the third category of antigenic determinants. They are unique to the molecules produced by a given clone of antibody-producing cells. Idiotypes are formed by the unique structure of the antigen-binding portion of the molecule.


Antibody molecules (Fig. 314-8) are composed of two heavy chains (∼50,000 mol wt) and two light chains (∼25,000 mol wt). Each chain has a constant portion (limited amino acid sequence variability) and a variable region (extensive sequence variability). The light and heavy chains are linked by disulfide bonds and are aligned so that their variable regions are adjacent to one another. This variable region forms the antigen recognition site of the antibody molecule; its unique structural features form a particular set of determinants, or idiotypes, that are reliable markers for a particular clone of cells because each antibody is formed and secreted by a single clone. Each chain is specified by distinct genes, synthesized separately, and assembled into an intact antibody molecule after translation. Because of the mechanics of the gene rearrangements necessary to specify ...

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