Idiotype‐bearing and antigen‐binding receptors produced by blood T lymphocytes in a case of human myeloma

Abstract

Idiotype-bearing and antigen-binding receptors produced by blood T lymphocytes in a case of human myeloma"Twenty-five t o 30 % of blood lymphocytes from a myeloma patient with an IgGl(K) protein with antibody activity to horse a2-macroglobulin (a2M) reacted with purified IgG from a rabbit antiserum t o the idiotypic determinants of this protein. A small proportion of these idiotype-bearing lymphccytes were IgG-bearing B cells, but most of them were T cells. Several experiments demonstrated the actual synthesis of the idiotypic structures carried by the T lymphocytes. All idiotype-bearing lymphocytes bound horse a2M, and the structures that bore the idiotype and bound the antigen were shown t o completely cocap. After biosynthetic labeling with I4C-labeled amino acids, immunoprecipitation and sodium dodecyl sulfate gel electrophoresis, the antiidiotypic serum and the a2M antigen were found t o react with the same molecules. Preliminary data & the size of these antigen-binding T lymphocytederived molecules are in accord with those of Binz and Wigzell ( S c u d . ; I . Immunol. 1976. 5: 559) in the rat. The finding in this patient with multiple myeloma of a homogeneous and possibly malignant population of T lymphocytes, synthesizing identical antigen receptors which share idiotypic (but not isotypic) determinants of the immunoglobulin molecule produced by the malignant B cell clone, therefore confirms in man the results of several recent studies in other mammalian species. Abbreviations: PBL: Peripheral blood lymphocytes IBL: Idiotypebearidg lymphocytes; lymphocytes bearing (and synthesizing) the same idiotypic determinants as those of the serum myeloma protein SIg: Surface immunoglobulins a2M: ~~2-Macroglobulin RFC: Rosette-forming cells SDS: Sodium dodecyl sulfateThe presence, in human and murine myelomas, of peripheral blood lymphocytes (PBL) bearing on their membrane molecules which react with antisera specific for the individual myeloma protein idiotypic determinants, has been reported by several groups [l-41. The fact that these molecules were actual cell products was demonstrated by their regrowth after stripping of the membrane by proteolytic enzymes [3-51.Blood lymphocytes which carry the idiotypic determinants of the myeloma protein, here referred t o as "idiotype-bearing lymphocytes" (IBL), were considered t o be B cells. This interpretation is supported by our finding, in about one third of untreated myeloma patients, of "monoclonal" populations

In vitro idiotypic suppression of chronic lymphocytic leukemia lymphocytes secreting monoclonal immunoglobulin M anti-sheep erythrocyte antibody.

“…This is of interest in that other data have indicated that tolerance induced by antigen or antibody (allotypic suppression) could be broken by polyclonal B-cell activators (24,25). It should be pointed out, given the report of idiotypic determinants on T cells (26) …”

Molecular characterization of a somatically mutated anti-DNA antibody bearing two systemic lupus erythematosus-related idiotypes.

“…We have previously found by protein sequence analysis that 31-reactive light chains from different patients can be encoded by VK genes of more than one gene family (35). The presence of nontransformed B cells in the bone marrow of patients with myeloma that are idiotypically related to the myeloma cells have been reported by several laboratories (21)(22)(23). Although it has been suggested that these are precursors to the myeloma cell, it is possible that they represent multiple independent clones activated by an idiotypic network.…”

Severe deficiency of B lymphocytes in peripheral blood from multiple myeloma patients.

“…(7)(8)(9)(10)(11)(12)(13)(14). Both an expanded monoclonal lymphocyte pool and an absence of monoclonal lymphocytes related to the malignant plasma cells have also been reported (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”