W. Hijmans

The origin of monomeric and polymeric forms of IgA in man

A distinctive feature of immunoglobulin A is its tendency to occur in different molecular forms. In contrast to that in most mammalian species, the majority (85 to 90%) of the serum IgA in man occurs in a monomeric form. This prompts a question as to where the monomeric and the polymeric serum IgA is formed and by which cells. Peripheral lymph nodes, spleen, and intestinal lymphoid tissue have long been considered the main sources of circulating IgA (1). However, Hijmans et al. (2) have shown that human bone marrow, because it carries such a large number of cells that contain IgA, can be regarded as a major source of the circulating IgA. Test systems at the cellular level which specifically distinguish between the different molecular forms of IgA may help to clarify this problem.

The Formation in vitro of Paraproteins in Multiple Myeloma and Waldenstrom's Macroglobulinaemia

THE sera of patients suffering from multiple myeloma or Waldenstrom’s macroglobulinaemia are characterized by the presence of electrophoretically homogenous peaks of immunoglobulins. These proteins, called paraproteins (Apitz, 1940), can belong to any one of the four classes of human serum immunoglobulins (Heremans, 1959; Rowe and Fahey, 1965). On the basis of the antigenic determinants residing on the L-chain, designated type K and type L, the normal immunoglobuhs, paraproteins, and Bence-Jones proteins can be classified into two groups of molecules (Korngold and Lipari, 1956; M a d and Kunkel, 1963a, b; Fahey, 1963a, b, c; Fahey and Solomon, 1963 ; Migita and Putnam, 1963). Normal sera contain both types of molecules, although the ratio of type K to type L molecules of the isolated antibodies may differ significantly from that present in the normal serum (Mannik and Kunkel, 1963a, b; Fr& and Fudenberg, 1964). The paraproteins, like the individual Bence-Jones proteins, have the characteristic of containing only molecules belonging either to type K or type L. The literature on this subject has been covered in detail in recent reviews (Putnam and Hardy, 1955; Osserman, 1959; Fahey, 1962; Osserman and Takatsuki, 1963 ; Porter, 1963 ; Franklin, 1964; Tomasi, 1966). Paraproteinaemia is not exclusively associated with multiple myeloma and Waldenstrom’s disease, but is occasionally also found in various other diseases such as chronic lymphatic leukaemia, lymphosarcoma, carcinoma, cirrhosis of the liver, rheumatoid arthritis, chronic infections, and in apparently healthy persons (Azar, Hill and Osserman, 1957; Owen, Pitney and O’Dea, 1959; Waldenstrom, 1961, 1962,1964; Hallin, 1963 ; Marki and Wuhrmann, 1963 ; Ossermanand Takatsk, 1963 ; Imhof, Bauieux, Poenand Mul, 1964; Andersen, 1964; Fine, Ennuyer, Helary and Ridremont, 1964; Gothoni, Wasastjerna and Jeglinsky, 1965; Osserman, 1965; van Furth, Schuit, HlJmans and Huibregtse, 1966; van Furth, Schuit and Hijmans, 1966~). Extensive studies on the formation of myeloma proteins in vitro by transplantable mouse plasma cell tumours have been reported (Askonas, 1961 ; Askonas and Fahey, 1961 ; Thorbecke, Hochwald and Jacobson, 1962). The formation of G paraprotein by human tissues in vitro has been reported in a case of multiple myeloma with a plasma-cell leukaemia, in which peripheral blood was cultured (Sonnet, Gillant and Sokal, 1958) and ina bone-marrow culture (Seligmann, Danon and Huriez, 1963), as well as the formation of Bence-Jones proteins in a bone-marrow culture (Meyer, 1962). The synthesis of macroglobulins in vitro by lymph nodes of patients suffering from Waldenstrom’s macroglobulinaemia has also been published (Zucker-Frankh, Fra& and Cooper, 1962). The cellular localization of paraprotein formation in man has been investigated by immunofluorescent staining of bone-marrow biopsy samples and lymph nodes. These studies have

Microfluorometric evaluation of the specificity of fluorescent antisera against mouse immunoglobulins with the defined antigen substrate spheres (DASS) system.

Highly purified MOPC-21 IgG1, MOPC-173 IgG2a, MOPC-195 IgG2b, MOPC-104 E IgM, and MOPC-315 IgA paraproteins, heterogeneous mouse IgG, Fab and Fc fragments of heterogeneous IgG were prepared and coupled to Sepharose beads. These beads were then used as artificial substrates to test the specificity of fluorescent antisera against mouse immunoglobulins by microflurometry. By comparing the visual evaluation of strained plasma cells and measurements on beads, the highest permissible percentage (FITC) and 6% for a tetramethyl rhodamine iso thiocyanate (TRITC) conjugate. By application of these criteria, 1 out of 7 tested commercial antisera and 6 out of 8 conjugates prepared in this laboratory proved to be satisfactory. The most common impurities were anti-light chain antibodies, as revealed by their reaction with Fab. With the bead system, a good impression of the specificity of an antiserum can be obtained. It gives, however, only approximate information on whether the conjugate will cause a high background staining in the biological specimen.

Intracellular immunoglobulin G ‘Pseudocrystals’ in a patient with chronic B-cell leukemia

A patient with chronic B‐cell leukemia in whom the malignant lymphocytes showed intracellular inclusions of immunoglobulin (Ig) G kappa molecules is described. Electron microscopy revealed filamentous material in the nuclear envelopes and in the cisternae of the rough endoplasmic reticulum. These in vivo surface Ig‐negative, nonexcreting cells could be stimulated in vitro to excrete immunoglobulin‐free light chain molecules into the supernatant, which were not found in the cytoplasm after stimulation. Cancer 58:43–51, 1986.