In Which Cells Does Neoplastic Transformation Occur in Myelomatosis?

Abstract

Myelomatosis is strictly a neoplasm of plasma cells in bone marrow. It does not involve other sites of antibody production; thus, even when the monoclonal protein produced by the neoplastic clone is IgA1 or IgA2 the neoplastic cells are not found in the lamina propria of the gut (Leonard et al 1979). Importantly the production of an IgM paraprotein by the neoplastic cells is vanishingly rare, amounting to only 0.2 % of 2011 successive patients admitted to MRC myelomatosis trials. IgG paraproteins were found in 57.2 % (0.15% with IgG with a minor IgM paraprotien of the same light chain isotype), IgA in 27% (0.10% with IgA with a minor IgM paraprotein of the same light chain isotype), IgD in 1.5%, IgE 0.1%. Free light chains alone were produced by the neoplastic cells of 14% of patients and 1.8% had no paraprotein. Physiologically in the established phase of those T cell-dependent antibody responses where B cells are being activated in the spleen antibody production takes place in the bone marrow (Benner et al 1981). This also applies to responses in those lymph nodes which do not receive lymph from mucosal surfaces. It has been shown in rodents that the B cells are activated in the follicles of these secondary lymphoid tissues (Tew et al. 1992) and migrate via the lymph and/or blood to the marrow. Migrant plasmablasts can be found in the blood of healthy humans. Analysis of the life-span of bone marrow plasma cells in rats indicates that IgG-or IgA-secreting plasma cells survive for about a month (Ho et al 1986). Conversely the IgM-producing plasma cells in the marrow like most plasma cells in the spleen and lymph nodes, irrespective of the class of Immunoglobulin produced, live for only 3 days (Ho et al 1986). It may be that these IgM-producing cells have been generated by local activation of B cells at the surface of macrophages by T cell-independent antigens (Corbel and Melchers 1983). Normal human bone marrow does not contain obvious secondary lymphoid tissue so it seems likely that the IgG and IgA plasma cells in this tissue are also derived from distant secondary lymphoid tissues. (Studies of plasma cells from the bone marrow from patients with rheumatoid arthritis as a means for investigating the physiological equivalent of neoplastic cells in myelomatosis could be misleading; for the marrow in this disease contains well-developed secondary lymphoid tissue).