Idiotypic Uniformity of Cell Surface Immunoglobulin in Chronic Lymphocytic Leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is thought to be a malignancy of bone marrow-derived (B) lymphocytes, since the leukemic cells from a majority of patients bear easily detectable membrane-bound immunoglobulin (Ig) (1), possess a complement (C3) receptor (2), and do not bind sheep erythrocytes (3). Since in most studies (1, 3-5), but not all (6), the cells from an individual patient bear Ig restricted to a single light chain class, it is suspected that the CLL lymphocytes represent the progeny of a single clone of B cells.The present study provides support for the clonal proliferation of CLL cells by demonstrating in a single patient that the Ig on virtually all of the CLL cells possess the same idiotypic (variable region) determinants. The anti-idiotypic serum, prepared against a circulating paraprotein, reacted only with the paraprotein and the surface Ig on the CLL cells and not with a variety of other serum or cell-bound Igs. Materials and MethodsSource and Isolation of Lymphocytes. J . T . is a 61-yr old male with an 18 mo history of chronic lymphocytic leukemia and an |gG paraprotein. The peripheral lymphocyte count has been maintained at _< 20,000 mature lymphocytes per mm 3 by two, brief courses of chemotherapy. The IgG paraprotein has persisted at 50-60 mg/ml throughout his course.Lymphocytes were collected from peripheral blood by the methods of BSyum (7). CLL lymphocytes from 23 different patients were either used fresh or frozen viably (8) and stored at -82°C for periods of up to 9 mo before use. Viability of the thawed cells ranged from 40-82%. Preliminary experiments demonstrated that viably frozen cells maintained their surface immunoglobulin. Lymphocytes (PBL) from 16 nonhematologic patients were used fresh.

Idiotypic Lymphocytes in the Rabbit: Occurrence and Nature of Idiotypic Lymphocytes in Normal and Hyperimmunized Rabbits

“…In normal rats and mice idiotypic structures associated with recognition of alloantigens have been located on the surface of both B cells and T cells [6,22,29], In some patients with Bcell malignancies (chronic lymphatic leukaemia (CLL) and multiple myeloma), idiotypic structures have been found, primarily on the surface of B cells [17,30,31] although some workers could also detect them on T cells [28]. In normal and immunized mice, idiotypic structures with antibody activity against heteroantigcns are demonstrable on the surface of T and B lymphocytes by ftinctional assays [12.…”

Waldenström‐like Lymphoma with Monoclonal IgG1kappa: Evidence of Common Clonal Origin

“…The main proliferation occurs at the plasma cell level, situated in the bone marrow, and will lead to the clinical symptoms. A comparable situation is seen in chronic lymphocytic leukaemia with M-component, where some of the neoplastic lymphocytes mature and give rise to a small population of bone marrow plasma cells, secreting the monoclonal immunoglobulin (Salmon 8i Seligmann, 1974;Schroer et al, 1974;Aisenberg et al, 1973;Stein et al, 1977;Sugai etal, 1978).…”

Immunotherapy of B lymphoma by anti-idiotype antibodies: Characterization of variant tumour cells appearing a long time after the initial tumour inoculation

“…These lymphoma cells possess IgM molecules on their surface, which are unique for each tumour, by virtue of their unique idiotypic determinants [8,15,38,39,41]. As these determinants are tumour-specific antigens [8], they can serve as immunotherapeutic targets [14,15,28].…”

“…Most B lymphoma tumours in humans and experimental animals are monoclonal [22,32,37,45], express unique VH and VL and have, therefore, unique idiotypic (Id) determinants [8,15,38,39,41]. It has been previously reported that in some cases of lymphoma patients and murine B-cell tumours, subpopulations of tumour cells developed that Offprint requests to: M. Taya had lost the idiotypic determinants expressed on the cell surface of the original lymphoma cells [10-12, 27, 40, 42].…”