ABSTRACT
Plasma cell disorders are characterized by a proliferation of clonal B lymphocytes at various stages of maturation and by plasma cell infiltration of the bone marrow. The monoclonal immunoglobulin (Ig) (the ‘M component’) produced by the clonal B cells has unique variable regions in the heavy and light chains. B cells belonging to the tumor clone can be identified by their cell surface expression of the monoclonal Ig that carries the same idiotype as the M component.1 Such monoclonal B cells are present in the bone marrow as well as in peripheral blood. The presence of circulating monoclonal B cells in the peripheral blood in myeloma and monoclonal gammopathy of undetermined significance (MGUS) has been confirmed by cytogenetic analysis.2 Clonal rearrangement of Ig heavy-and light-chain genes has been demonstrated in blood lymphocytes and bone marrow plasma cells by Southern blot analysis.3 Using highly sensitive polymerase chain
lymphocytes have been detected in almost all patients with myeloma, although the reported frequencies differ significantly.4-6
Idiotype structures present on the secreted M component and on the surface Ig of clonal B cells are tumor-specific antigens; as such, they are potential targets for specific anti-idiotype immunity.7 Myeloma B lymphocytes are mature B cells. They may express, on the cell surface, idiotypic Ig as well as major histocompatibility complex (MHC) class I and II molecules, and are sensitive to regulatory signals provided by cellular and humoral components of the idiotype-specific immune network (Figure 6.1). The majority of the tumor cells in myeloma, however, are the bone marrow plasma cells, which may not express surface Ig. Myeloma plasma cells secrete the M component and express cytoplasmic Ig (cIg). It has been shown that cIg in mouse B-cell lymphoma and plasmacytoma cells is processed intracellularly, and that degraded idiotypic peptides are presented on the cell surface in the context of MHC molecules.8 Moreover, myeloma plasma cells may express MHC class I antigens,9,10 adhesion molecules (e.g. CD44, CD56, CD54 and VLA-4),11,12 and the signaling or
CD28,10,13,14 as well as the Fas antigen (CD95).15
