Anti-idiotypic immunity in multiple myeloma and monoclonal gammopathy of undetermined significance

Monoclonal gammopathies such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are lymphoproliferative B cell diseases. B cells/plasma cells produce the monoclonal immunoglobulin (Ig) which can be detected in plasma and/or urine. Such Ig have unique variable regions of the heavy and light chains and may be regarded as tumour-specific antigens and as such potential targets for immune regulation of the tumour cell clone, by anti-idiotype (Id) immune reactions. The production of anti-Id Ab against the M-component by primary B cell lines of Epstein-Barr virus transformed PBMC was analysed in patients with MM and MGUS. Patients with advanced disease (MM stage III) had a low and patients with MM stage I and MGUS a high production of such anti-ld Ab (p<0.0 1). Anti-Id B cells were studied in patients with MM, MGUS and in healthy controls using an ELISPOT assay. All patients had B cells producing Ab to F(ab+)2 fragments of autologous and allogeneic M-components. There was no difference between patients with MM and MGUS with regard to the number of B cells producing Ab against autologous M-component. MGUS and MM patients had autoreactive B cells more frequently than alloreactive B cells (p<0.00 1). The number of alloreactive B cells did not differ between patients and controls. T cells reactive with F(ab+)2 fragments of autologous and allogeneic M-components were analysed in patients with MM, MGUS and in healthy controls using an ELISPOT assay. In patients, the number of T cells that were stimulated by autologous M-component was higher (p<0.01), than the number of cells activated by allogeneic Ig. Subpopulations of Id-reactive T cells were defined by demonstrating Th cells with different cytokine-secreting patterns after stimulation by F(ab+)2 fragments of autologous M-components using ELISPOT assays. ThI -type cells (secreting IFN-y and IL-2) were more frequent in patients with a low tumour burden. Th2-type cells (secreting IL-4) dominated in patients with MM stage II-III. The T cell response was MHC class II-restricted. Id-reactive T cells were also demonstrated in MM and MGUS patients with 3H-thymidine-incorporation. The proliferation of cells was higher when stimulating PBMC with F(ab+ )2 fragments of autologous M-component (p