Transplantable in Mice

Antibody and y-globulin are formed by a number of tissues with highly heterogeneous cell populations such as bone marrow, lymph glands and spleen. Only a small part of the cells in these tissues are plasma-type celLs in which antibody protein and at least some ofthe y-globulin normally found in serum originate. This makes a study of globulin synthesis difficult. Recently, Dr M. Potter and his collaborators at the National Cancer Institute, Bethesda, have established several lines of plasma-cell tumours transplantable in inbred strains of mice. Each plasma-cell neoplasm is associated with different but characteristic globulins in high concentrations in the serum (Potter & Fahey, 1960). On electrophoresis of the serum at pH 8-6 these globulin migrate in the region of serum yand ,-globulin. The condition in mice shows great similarity to the human malignant disease, multiple myeloma. The tumour cells are basophilic cells with vacuoles and acentric nuclei characteristic of plasma cells normally found in lymphoid tissue (Dunn, Potter, Fahey & Merwin, 1960). Electron micrographs of thin sections show that the cell cytoplasm has a highly organized endoplasmic reticulum (A. J. Dalton, unpublished work) similar to that found in hepatic or pancreatic cells and normal plasma cells. This organization is characteristic of cells active in protein formation and secretion. The subcutaneous mouse tumours provide tissue to study the synthesis of globulin in vitro and make it possible to follow globulin formation by plasma cells over many transplant generations. One of the plasma-cell neoplasms (5563) has been studied in detail, since the globulin in the serum of animals bearing the 5563 tumour was found to be very similar to normal mouse y-globulin in its immunological properties. It is referred to below as y-globulin or y-myeloma protein. Dr B. Balfour at this Institute stained sections of the 5563 tumour with fluorescein-labelled rabbit antibody against purified myeloma protein. Almost all cells showed a highly fluorescent cytoplasm and therefore contained myeloma protein. The tumour tissue thus provides us with a fairly homogeneous population of plasma cells. In the work described in this