Richard Asofsky

Major urinary protein complex of normal mice: origin.

Mouse serum contains protein having the same charge density and molecular size as the major urinary protein complex of mice. Mouse liver (but not eight other tissues examined) incorporated amino acids labeled with carbon-14 into the complex in vitro. The degree of incorporation was greater in livers from males than from females, and was internmediate in livers from females treated with testosterone.

Immunoglobulin synthesis by salivary gland lymphoid cells in Sjögren's syndrome

The synthesis of immunoglobulins by cells infiltrating the labial salivary glands has been studied by radioimmunoelectrophoresis in 20 patients with Sjögrens syndrome (SS) and in 14 control patients with related disorders. The patients with SS were producing significantly greater quantities of IgG, IgM, and IgA. Synthesis of IgG and IgM correlated with the degree of lymphoid infiltration but not with serum immunoglobulin concentration. Patients with SS and rheumatoid arthritis (RA) showed greater synthesis of IgG and IgM than those with uncomplicated RA. The only extensive lymphoid infiltration was seen in patients with SS. One patient with SS and primary macroglobulinemia was synthesizing the paraprotein in the lip biopsy as well as in the bone marrow. These results establish the immunologic competence of the infiltrating lymphoid cells and suggest their origin from an extrasalivary source.

Salivary gland immunoglobulin and rheumatoid factor synthesis in Sjögren's syndrome: Natural history and response to treatment

Abstract Labial salivary glands, like the major salivary glands, are infiltrated with lymphoid cells in Sjogrens syndrome (SS). Studies utilizing biopsy specimens from the lower lips of seventy-six patients, forty-one of whom had Sjogrens syndrome, demonstrated that local synthesis of large amounts of immunoglobulins (IgM and IgG) and rheumatoid factor in salivary glandular tissue is distinctive for Sjogrens syndrome. The presence of rheumatoid factor was demonstrated autoradiographically by interaction between anti-lgG:lgG complexes and labeled immunoglobulins. Rheumatoid factor in the lip was found in eighteen of forty-one (43 per cent) patients with Sjogrens syndrome and in only two of thirty-five (6 per cent) control patients. On repeat biopsy of the lip untreated patients showed progression of lymphoid infiltration and increased immunoglobulin synthesis, whereas two patients treated with cyclophosphamide showed improvement histologically and all treated patients had diminished immunoglobulin synthesis. Sicca symptoms diminished in five of ten patients who were treated with cyclophosphamide for serious complications or other associated diseases, but immunosuppressive therapy cannot yet be recommended for uncomplicated Sjogrens syndrome.

Macroglobulin-Producing Plasma-Cell Tumor in Mice: Identification of a New Light Chain.

A transplantable plasmacell tumor in mice produces both a γM-macroglobulin serum protein with a sedimentation coefficient of 17S and a kappa-type urinary protein. The reduced and alkylated macroglobulin, when examined by electrophoresis in acid-urea polyacrylamide gel, had a fast component which migrated in the same position as the urinary protein and also a slow component. These two components, as shown by exclusion chromatography, represent the light and heavy polypeptide chains of the γM-macroglobulin. The aforementioned macroglobulin was antigenically related to that in normal mouse serum.

Cell Interactions in the Graft-versus-Host Response

Publisher Summary This chapter presents a study analyzing the cell interactions in the graft-versus-host response. Adult male BALB/cAnN, C57BL/6N, and F1 hybrid mice of these strains, as well as newborn F1 hybrid and parental strain mice were obtained. Adult mice served as donors of cells and newborn mice as recipients. Cell suspensions from spleens and thymi were prepared. Peripheral blood was collected from the severed femoral artery into pipettes rinsed with heparin; blood leukocytes were separated by sedimentation in dextran solution. Fifty percent (±6%) of the original leukocyte number was recovered. Recovered cells consisted of more than 90% lymphocytes. Cells were injected intraperitoneally in a constant volume of 0.05 ml. When combinations of cells were used, the cells were mixed just prior to inoculation. The chapter also discusses reactions produced by combining different numbers of blood lymphocytes with 5 × 106 thymus cells. As few as 12,500 blood lymphocytes were sufficient to cause a detectable reaction in combination with thymus cells; larger numbers of PBL gave substantial reactions when combined with thymus cells.

Immunoglobulin isotype distribution of malaria-specific antibodies produced during infection with Plasmodium chabaudi adami and Plasmodium yoelii

The antibody response of mice to Plasmodium chabaudi adami and Plasmodium yoelii has been compared using a solid phase isotype-specific radioimmunoassay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Serological cross-reactivity between these parasites was substantial. Studies using a radioimmunoassay detecting all classes of malaria-specific antibody demonstrated that during the early part of infection it was not possible to distinguish between homologous and heterologous reactions. Immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that 50% or more of the protein antigens detected were apparently shared by both parasites although the intensity of bands was always greater with homologous reactions. However, the distribution of isotypes in the antibody (Ab) response differed in the two infections. P. chabaudi infections were characterized by a predominant and persistent IgM response, moderate IgG2 and IgG3 and little significant IgG1 response during a primary infection. By contrast, IgM antibodies were transient in P. yoelii infection, IgG2 was the predominant isotype, and both IgG1 and IgG3 antibodies were present during a primary infection. These differences in isotypes were also detected when sera were tested on the heterologous antigen extracts suggesting that antigens shared by P. chabaudi and P. yoelii do not necessarily induce similar antibody responses in the two infections.

The Mechanism of the Antitumor Action of Poly I: Poly C

We have already reported RNA, po1yinosinic:polycytidylic acid, (poly 1:poly C) exerts inhibitory action on a number of experimental tumors i n animals. were of three types; (1) a decrease i n growth ra te o f the tumor when treatment was s ta r ted a few days a f t e r implantation of the tumor, (2 ) regression of already well established tumors, (3) increased survival time i n the animals bearing the tumors. Table 1 gives a l i s t of most of the tumors examined. In addition, w i t h Dr. Herman duBuy, we have examined a melanoma, the Bittner mamnary tumor, the Ehrl i ch asci t es tumor, and have found comparable resul ts .

The dynamics of antibody secreting cell production: Regulation of growth and oscillations in the response to T-independent antigens

We present an interpretation and analysis of the dynamic structure of the response of antibody secreting cells to T-cell independent antigens. The observations of interest are sustained synchronous cycles in the number of such cells, and the discontinuous, “staircase” like increase in cell numbers during the first few days of the response. The main features of the model from which these results can be deduced are the existence of time delays which separate different cellular events, a particular distinction between proliferative and differentative events among the cells which will ultimately secrete antibody, and inhibition of the stimulation of the precursors of these cells by antibody already formed. In addition to describing various characteristics of cyclical antibody production, the model makes a variety of predictions related to its principal hypotheses, including the effects of antibody passively given or withdrawn on the kinetics and magnitude of the subsequent antibody response. The model also predicts, consistent with observation, the existence of an optimal dose of antigen, high and low zone unresponsiveness, and high zone tolerance. It is consistent with the phenomenon of maturation of affinity of antibody, and also predicts fluctuations in affinity. A study of the mathematical properties of the model indicates that for a wide range of parameters, the system possesses multiple steady states and limit cycle behaviour. Variations in concentrations of antigen and antibody are found to have a small influence on the frequency of oscillations, but a large influence on their amplitude.

Ontogeny of B lymphocytes: I. In vitro appearance of Ig-bearing lymphocytes

Abstract During the immediate postnatal period, a striking increase in the fraction and number of splenic lymphocytes which bear easily detectable surface immunoglobulin (Ig) occurs in BALB/c and CDF1 mice. Thus, in mice

Extinction of B-cell surface differentiation markers in hybrids between murine B-lymphoma and myeloma cells

Abstract Fusion between murine B-lymphoma cells bearing membrane IgM with either IgG or light chain secreting myeloma, resulted in cell hybrids synthesizing and secreting large quantities of IgM. In contrast, the hybrids did not secrete IgD even though it is also present on the surface of the B-lymphoma cells. B-Cell surface markers such as the IgM, IgD, Ia and the Fc receptor, which were present on the B-lymphoma cells, but not the myeloma cells were not expressed on the surface of the hybrids. Hybrids which secrete IgM and retain the B-cell membrane differentiation antigens were not detected, even when selection was done under conditions which favor the growth of the lymphoma parental cells.