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Biomedical subjects

R Asofsky

Publications and source records attributed to R Asofsky.

At least 55 records · Page 3Linked to original sources
PubMed1981

Chromosome 15 trisomy in spontaneous and carcinogen-induced murine lymphomas of B-cell origin.

G-banding analyses of 14 independently derived B-cell lymphomas showed the frequent occurrence of chromosome 15 trisomy. It was present in seven of nine spontaneous B-cell lymphomas, but in company with other trisomies, monosomies and marker chromosomes. In five carcinogen-induced primary B-cell leukemias, trisomy 15 was the dominating change. Taken together with the previously demonstrated importance of chromosome 15 trisomy for T-cell leukemogenesis and of the 12;15 translocation in plasmacytogenesis in the mouse, it appears likely that the distal part of chromosome 15 carries a cluster of genes, perhaps a supergene region, that may play an important role in the differentiation and/or the normal responsiveness of various lymphoreticular cell types to growth control.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Membrane immunoglobulins of spontaneous B lymphomas of aged BALB/c mice.

Four cell lines derived from spontaneous BALB/c lymphoma tumors were analyzed with regard to the type of their membrane immunoglobulins (Ig). Using lactoperoxidase iodination of membrane proteins combined with immunoprecipitation and electrophoresis on polyacrylamide gel, three of these cell lines (X16c, L10A and K46) were found to express the monomeric form of IgM and IgD as well as half molecules. One cell line (M12) lacked both IgM and IgD. The apparent mol. wt of the lymphoma micro chain was about 80 000 and exceeded the mol. wt. of 75 000 determined for micro chains secreted by myeloma cells. The mol. wt. of the delta heavy chain was found to be 66 000. Immunofluorescence showed that the L10A and X16c lines expressed lambda light chains on their cell surface. Another Ig-bearing cell line (K46) expressed both lambda and kappa chains. Thus, three out of the four B lymphomas examined expressed both IgM and IgD with light chains of the Lambda type. These results, together with our previous findings which demonstrate the presence of Ia and Fc receptors on the same cells, indicate that spontaneous B lymphomas in BALB/c mice are the malignant counterpart of mature B lymphocytes.

Aging↗
PubMed1981

T cell regulation of isotype expression. The requirement for a second Ig-specific helper T cell population for the induction of IgG responses.

A characteristic of the in vivo responses to T-dependent antigens is the highly restricted expression of Ig heavy chain classes of both the antibody and nonspecific Ig produced. To investigate the cellular interactions which regulate expression of Ig class, sheep red blood cell- and keyhole limpet hemocyanin-primed BALB/c T cells were tested in vitro for their ability to induce normal BALB/c B cells to selective Ig secretion. The results, based initially on linear regression analysis, indicate that while the production of IgM required help from a single antigen-specific helper cell, additional signals from a second pool of helper cells were necessary for the expression of IgG isotypes. The greatly diminished ability of primed T cells from mice suppressed from birth for IgM production to induce IgG responses indicated that the generation of this second class-regulating T cell pool requires the presence of Ig, probably B cell-presented, during the period of priming. Bases on the present data, secretion of IgG by normal B cells can be explained by invoking the requirement for a second pool of helper T cells which recognize Ig determinant, in contrast to the I region recognition known to exist for effective help by the first helper cell. In addition, it is proposed that in the absence of such a second signal only IgM secretion will occur.

Animals↗
PubMed1981

Monoclonal antibodies to stage-specific, species-specific, and cross-reactive antigens of the rodent malarial parasite, Plasmodium yoelii.

Eighteen hybridoma cell lines were used to study species-specific, stage-specific, and serological cross-reactive antigens of the rodent malarial parasite, Plasmodium yoelii. Specificity and location of plasmodial antigens were determined by indirect fluorescent-antibody analysis. Results showed that a minimum of 12 distinct plasmodial antigens could be distinguished by the 18 hybridomas. Antigens were found on the surface or within the cytoplasm of the parasite, but not on the surface of erythrocytes from infected animals. The majority (11 of 12) of antigens were present in all erythrocytic stages of the parasite, but one was stage-specific for merozoites. Additional studies showed that 6 of 18 of the monoclonal antibodies identified species-specific antigens, 2 of 18 recognized antigens confined to related rodent malarial parasites (Plasmodium berghei, Plasmodium vinckei, and Plasmodium chabaudi), whereas 8 of 18 detected cross-reactive antigens common to rodent, primate (Plasmodium knowlesi, Plasmodium falciparum), and avian (Plasmodium gallinaceum) malarias.

Animals↗
PubMed1981

Monoclonal antibodies against a specific surface determinant on malarial (Plasmodium knowlesi) merozoites block erythrocyte invasion.

Twelve hybridoma cell lines secreting monoclonal antibodies against Plasmodium knowlesi merozoites have been produced. Antibodies from 3 of the 12 lines agglutinated merozoites. The 2 monoclonal antibodies (13C11 and 16F8) that markedly agglutinated merozoites blocked merozoite invasion of erythrocytes. Of these 2 lines, the one that induced the most agglutination also blocked invasion most effectively. The third monoclonal antibody (53B3) caused minimal agglutination of merozoites and did not block invasion, nor did the other 9 nonagglutinating antibodies. The 2 blocking monoclonal antibodies bound to antigens around the entire surface of merozoites, as demonstrated by immunoelectron microscopy, and precipitated a single biosynthetically labeled protein of apparent m.w. of 250,000. None of the nonagglutinating lines precipitated this protein. Monoclonal antibodies 13C11 and 16F8 reacted with a common antigenic determinant on a Malaysian and a Philippine strain of P. knowlesi in that they blocked invasion and precipitated a 250,000 m.w. protein from both. Sera from immune monkeys also precipitated this 250,000 m.w. protein.

Agglutination↗
PubMed1980

Suppression of spontaneous reticulum cell sarcoma development and of syngeneic stimulator cell by anti-mu treatment of SJL/J mice.

The cellular origin of reticulum cell sarcoma (RCS) in SJL/J mice was studied by comparing the incidence of spontaneous RCS in control mice and in mice suppressed with goat anti-mu Ig from birth on. At 10 months of age anti-mu suppressed mice had 0% RCS as opposed to 60% in control mice. Growth of two i.v. injected transplantable RCS lines in anti-mu suppressed mice was approximately 60% as compared with growth in normal SJL/J mice. Proliferative responses of thymus and lymph node cells from anti-mu suppressed mice to RCS, mitomycin-treated syngeneic spleen cells (M. Spl.) Con A, and PHA were entirely normal. However, M. Spl. from anti-mu suppressed mice caused minimal or no stimulation of T cells from normal or anti-mu suppressed responders. The results suggest that the normal syngeneic stimulator cell is of B cell origin, either representing a direct precursor of RCS or indirectly influencing RCS appearance. A B cell origin of RCS is, furthermore, in agreement with some of its characteristics, such as surface markers (Ia antigens, Ly b) and in vivo localization properties.

Animals↗
PubMed1980

High anti-TNP plaque-forming cell potential of residual mIg+ cells in a T cell population.

In the course of experiments designed to study the immune response of purified populations of B lymphocytes to thymus-independent (TI) antigens, a variety of cell purification procedures were followed. In using anti-immunoglobulin-coated dishes to separate lymphocytes bearing membrane immunoglobulin (mIg) from mIg- lymphocytes, it was found that the nonadherent fraction, which was predominantly mIg-, complement receptor negative, and nonresponsive to the B cell mitogen lipopolysaccharide, gave very substantial anti-TNP plaque-forming cell responses to 2 TI antigens. These responses could be inhibited by incubation of such cells in the presence of anti-mu and thus appeared to be attributable to mIg+ cells. The evidence suggests the existence of a population of B lymphocytes that constitute a minor component of mIg+ cells having a high potential to make in vitro antibody responses. Users of techniques that utilize anti-Ig as a tool for separating B and T lymphocytes should carefully assess the extent to which residual B lymphocytes in the mIg- population contribute to antibody responses being studied.

Animals↗
PubMed1980

Differential binding of fluorescein-labeled lectins to mouse thymocytes: subsets revealed by flow microfluorometry.

Fluorescein-labeled lectins bound to mouse thymocytes were analyzed by flow microfluorometry. This technique has identified several lectins that bind differentially to thymocyte subsets. The most complex fluorescence distributions were obtained using lectins with nominal specificities for galactose or N-acetylglucosamine. Inhibition of binding by sugars confirmed that the fluoresceinated lectins were bound to cells at their carbohydrate binding site. Simultaneous analyses of lectin fluorescence and forward light scatter intensity showed that cell subpopulations of different sizes can exhibit marked differences in the level of binding such that the amount of lectin bound per cell is often independent of cell size. A minor population of dull or unstained cells, delineated by several of these lectins, correlates with the subpopulation of medium-sized thymocytes resistant to in vivo cortisone treatment.

Abrin↗
PubMed1980

A hybridoma from an autoimmune NZB/NZW mouse producing monoclonal antibody to ribosomal-RNA.

Spleen cells from an unimmunized autoimmune NZB/NZW F1 female mouse were fused to the BALB/c MPC-11 drug-resistant clone 45.6 TG 1.7. One hybrid clone (D4) produced IgG-3 immunoglobulin that bound ribosomal RNA. A high concentration of this antibody was produced in the ascitic fluid of NZB/NZW male mice. DNA, tRNA, and synthetic single- and double-stranded polynucleotides could not bind significantly to the antibody. A Scatchard analysis showed that the rRNA-binding immunoglobulin is monoclonal and has a high affinity (10(9) liter/mole) for the RNA antigen.

Animals↗
PubMed1980

Radioimmunoassay for detecting antibodies against murine malarial parasite antigens: monoclonal antibodies recognizing Plasmodium yoelii antigens.

A solid-phase radioimmunoassay (SPRIA) in microtiter wells was established for detecting antibodies against Plasmodium yoelii Ag. The SPRIA was found 1) to require as little as 5 micrograms of crude parasite Ag per well, 2) to be able to detect 0.5 ng of monoclonal Ab, and 3) to be 10(4) times more sensitive than the indirect fluorescent Ab staining technique. In a modification of the above assay using intact RBC as an Ag, hyperimmune serum showed significant binding to the surface of erythrocytes of mice infected with P. yoelii parasites but not to RBC of normal mice. Hybridomas were prepared by fusing infected mouse spleen cells with P3-NS1/I-Ag4-1 myeloma cells. Using the SPRIA, hybrids secreting Ab against P. yoelii 17XL Ag were detected. All the hybrids detected by SPRIA secreted Ab binding to free parasites but not to the surface membrane Ag on the infected RBC. The number of positive hybrids produced by fusing spleen cells from mice given a double infection (17XNL and 17 XL) was not greater than that produced by freezing spleen cells from mice given a single infection (17 XL).

Animals↗
PubMed1979

Synthesis of two classes of antibody, gammaM and gammaG or gammaM and gammaA, by identical cells. Amplification of the antibody response to pneumococcal polysaccharide type III.

Class-specific plaque-forming cell (PFC) (gammaM, gamma1, gamma2, and gammaA) responses to type III pneumococcal polysaccharide (SSS-III) were studied in BALB/c x C57BL/6F1 (CBF1) mice with and without induction of an allogeneic effect. Gamma1, gamma2, and gammaA PFC were detected in two ways: (a) With the sequential development of the assay slides, first for direct (gammaM)PFC followed by incubation with class-specific antiimmunoglobulin and complement for the development of additional gamma1, gamma2, and gammaA PFC (gammaM-independent gamma1, gamma2, and gammaA PFC); and (b) by blocking gammaM PFC with goat anti-gammaM and simultaneously developing gamma1, gamma2, and gammaA PFC (total gamma1-, gamma2-, and gammaA-secreting PFC). The results showed that whereas gammaM PFC arose on the 3rd d after immunization, gamma1-, gamma2-, and gammaA-secreting PFC arose on the 4th to 5th d after immunization. They appeared in association with gammaM-secreting PFC because they were detected with the gammaM blocking method but not with the sequential method. By the 7th d most gamma1, gamma2, and gammaA PFC were detected by the sequential method as well, indicating that those antibodies were secreted independently of cells secreting gammaM. When the numbers of double-class-secreting PFC were evaluated on the 5th d, the following results were obtained: 83% of gammaM PFC were secreting either gamma1 (25%), gamma2 (55%), or gammaA (2%). We interpret these data as evidence for an antigen-driven class differentiation from gammaM to gammaA and from gammaM to gammaG in the majority of anti-SSS-III-secreting clones without T-cell help. When an allogeneic effect was provided by inoculation of parental BALB/c spleen cells together with antigen, the numbers of all classes of PFC were increased. Furthermore, the frequency of gammaM-gammaG (108%) or gammaM-gammaA (9%) double-class secretors was increased, and gammaM-independent gammaG and gammaA secretors were detected earlier, indicating an overall maturation-promoting effect. In addition, prolonged appearance of gammaA PFC was dependent on the allogeneic effect.

Animals↗
PubMed1979

Induction of amplified synthesis and secretion of IgM by fusion of murine 'b lymphoma with myeloma cells.

Murine B lymphoma cultured cell lines bearing membrane IgM and lacking the ability to secrete measurable amounts of IgM were fused with drug-resistant cell lines derived from the IgG2b-producing MPC-11 myeloma. Many of the hybrid clones synthesized and secreted large amounts of IgM, as judged by radial and double immunodiffusion in agar of culture supernatants and by polyacrylamide gel electrophoresis of biosynthetically labeled IgM. When fused with an IgG2b-producing myeloma, many of the hybrids also produced IgG2b, indicating that there was no suppression of the parental IgG synthesis in the hybrids. The amount of IgM or IgG2b secreted by the hybrids was higher than that secreted by myeloma cell lines. The synthesis of the gamma2b heavy chain of the MPC-11 myeloma was not reexpressed by fusion of a gamma2b nonproducer myeloma cell variant with B lymphoma. No other classes of Ig heavy chains, besides the gamma2b and the mu chains, were found to be secreted by any of more than 100 B lymphoma--myeloma hybrids examined. The results of the present work suggest that myeloma cells may fuse not only with normal plasma cells but also with less-mature normal B lymphocytes and that this fusion "induces" the maturation of B lymphocytes into IgM-secreting cells.

Animals↗
PubMed1979

Murine plasma cells secreting more than one class of immunoglobulin. VI. Secretion of completely assembled IgG2b and IgA molecules with segregated heavy chains and free light chains by spontaneous myeloma SAMM 368 in culture.

The antigenic and molecular characteristics of the two immunoglobulins secreted by a single cell line of plasmacytoma SAMM 368 were analyzed by polyacrylamide gel electrophoresis of biosynthesized proteins. Adapted to continuous in vitro cultivation, this BALB/c plasmacytoma secretes at least 98% of its heavy chains as components of fully assembled and isotypically uniform IgG2b and IgA molecules. The IgA is secreted as monomers, dimers, and multimers with chemical properties typical of BALB/c myeloma IgA including disulfide bonded J chain and noncovalently bonded light chains. The noncovalently bonded light chains are monomers rather than dimers. Free light chains are also secreted. The ability to segregate heavy chains is attributed either to chemical, enzymatic, or compartmental regulatory factors operating within these plasma cells.

Animals↗