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Biomedical subjects

R Asofsky

Publications and source records attributed to R Asofsky.

At least 91 records · Page 5Linked to original sources

Murine plasma cells secreting more than one class of immunoglobulin heavy chain. II. SAMM 368--a plasmacytoma secreting IgG2b-kappa and IgA-kappa immunoglobulins which do not share idiotypic determinants.

SAMM 368 is a BALB/c plasmacytoma which secretes IgG2b-kappa and IgA-kappa paraproteins. Immunofluorescence studies of ascites cells from the tumor with purified, heavy chain class-specific antiglobulins demonstrate that single cells contain both IgG2 and IgA heavy chains. Idiotypic antisera prepared in mice and rabbits indicate that the two paraproteins produced by the tumor do not share idiotypic determinants. Analysis of the purified paraproteins for allotype markers showed that SAMM 368 IgA bears the BALB/c A12,13,14 determinants. SAMM 368 IgG2b does not carry any detectable allotypic determinants in spite of the fact that heterologous antisera identify the paraprotein as IgG2b.

Amino Acid Sequence↗

B-lymphocyte heterogeneity: ontogenetic development and organ distribution of B-lymphocyte populations defined by their density of surface immunoglobulin.

The density of total Ig and of IgM, IgG1, IgG2, and IgA on the surface of adult murine splenic B lymphocytes was measured using the technique of rapid flow microfluorometry. In addition, the density of total surface Ig and of IgM on B lymphocytes derived from adult bone marrow, lymph nodes, and Peyer's patches, and from neonatal spleen was determined. Adult spleen and lymph node B lymphocytes are characterized by the presence of a large population of cells with a low-to-intermediate density of total surface Ig, which is seen as a peak in the fluorescence profiles when these cells are labeled with fluorescein-conjugated (F1) anti-Ig. This peak is not detected when neonatal spleen or adult bone marrow are examined; the development of this peak among spleen cells occurs during the first 4 wk of life. Although the characteristic fluorescence intensity peak is not seen when adult spleen cells are labeled with Fl anti-mu, changes in the density of surface IgM do occur during the first few weeks of life and are detected as a decrease in the frequency of cells which have relatively large amounts of surface IgM. The differences seen in the fluorescence patterns of adult spleen cells labeled with Fl anti-Ig and Fl anti-mu may be due to the appearance of IgD on the surface of mature splenic B lymphocytes. This is supported by the similarity of the fluorescence profiles of adult bone marrow cells stained with Fl anti-Ig and Fl anti-mu, as the latter population of cells is reported to lack surface IgD.

Age Factors↗

Cell membrane IgD: demonstration of IgD on human lymphocytes by enzyme-catalyzed iodination and comparison with cell surface Ig of mouse, guinea pig, and rabbit.

A substantial fraction of human cord blood and peripheral blood lymphocytes have recently been shown to bear IgD. Although IgD has not been identified in mice, it has been suggested that it is also a major surface immunoglobulin of murine lymphocytes. Thus, lactoperoxidase-catalyzed iodination of surface immunoglobulin of mouse spleen and lymph node cells reveals the existence of an IgH chain differing from mu, gamma, and alpha-chain both antigenically and by mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This new H chain class has been previously proposed to be the mouse homologue of delta-chain. In this paper, we analyzed human, mouse, guinea pig, and rabbit lymphoid cell membrane Ig by lactoperoxidase-catalyzed iodination, extraction with non-ionic detergent precipitation with a variety of specific anti-Ig sera, and electrophoresis of dissolved reduced precipitates on sodium dodecyl sulfate-polyacrylamide gels. Our studies confirm the previous reports of a new mouse cell membrane H chain with a mobility more rapid than that of mu-chain. However, we fail to detect a molecule with this electrophoretic mobility on the surface of guinea pig or rabbit lymph node and spleen cells. Moreover, neither anti-kappa nor anti-delta antibody precipitates a molecule with an H chain of this mobility from labeled extracts of human cord blood or peripheral blood lymphocytes. Cell surface delta was identified on both human cord blood and peripheral blood lymphocytes, but it proved to have mobility similar to human and mouse mu-chain. This result indicates either that mouse delta-chain has an electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels which differs appreciably from that of human membrane delta-chain or that the newly described mouse H chain is not the homologue of human delta-chain.

Animals↗

Neonatal infection with mouse thymic virus. Differential effects on T cells mediating the graft-versus-host reaction.

Neonatal infection with mouse thymic virus (TA), a murine herpes virus, produced extensive but temporary necrosis of the thymus which was maximal at 10 to 14 days of age. Studies of precursor and amplifier cells mediating graft-vs-host (GVH) reactivity of thymocytes, spleen cells (SC), and lymph node cells (LNC) of normal and TA-infected mice were made at 4 and 8 weeks of age. Infection with TA resulting in a profound reduction (70 to 80%) in the direct GVH reactivity of thymocytes at both ages; by comparison, the capacity of thymocytes to produce synergy when combined with normal LNC was normal at 8 weeks. Direct GVH reactivity of SC was depressed 90% 4 weeks after infection with TA but returned to near normal at 8 weeks. Direct GVH reactivity of LNC from TA-infected mice was normal at 4 and 8 weeks of age, but amplifier T cell activity in LNC was markedly depressed at 8 wekks. These results demonstrate that TA has highly selective effects upon subpopulations of T cells in thymus and lymph node.

Animals↗

Murine plasma cells secreting more than one class of immunoglobulin heavy chain. I. Frequency of two or more M-components in ascitic fluids from 788 primary plasmacytomas.

Primary ascites from 778 consecutive plasmacytomas of BALB/c and other mouse strains were tested by immunoelectrophoresis for the presence of paraproteins belonging to different immunoglobulin classes. gammaA was produced by 338 tumors: gamma Gs (gamma 1, gamma 2a, gamma 2b, or gamma 3) by 163 tumors; and gamma M by seven tumors. Free kappa- or lambda-typed light chains were produced by 14 tumors, and no detectable paraprotein was produced by 202 tumors. Two or more paraproteins were detected in the primary ascites of 54 plasmacytomas. Evidence suggests that in most cases, the multiple paraproteins are produced by simultaneously occurring, independent plasma cell tumors. However, two tumors, SAMM 368 and TEPC 609, produced two paraproteins for over 30 generations in transplantation. This finding implies that single clones of plasma cells have the capacity to produce more than one class of immunoglobulin.

Animals↗

Sequential analysis of transplantable hepatocellular carcinomas.

In a previous study multiple characteristics of chemically induced primary hepatocellular carcinomas were described and examined during the initial transplant generations. The present communication reports on these characteristics in subsequent transplant generations followed over a 2-year period. In almost all instances the growth rate, morphology, chromosome composition, and plasma protein and alpha-fetoprotein synthesis of individual tumors have remained relatively constant. However, one spontaneous subline of a diploid tumor demonstrated a sudden extensive rearrangement of its chromosomes simultaneous with a significant acceleration of growth rate. Despite karyotypic evolution, it retained the functional characteristics of diploid tumors, producing no plasma protein or alpha-fetoprotein.

2-Acetylaminofluorene↗

Genetic control of the antibody response to type 3 pneumococcal polysaccharide in mice. II. Relationship between IgM immunoglobulin levels and the ability to give an IgM antibody response.

Serum IgM immunoglobulin levels and antibody responses to an optimally immunogenic dose of Type III pneumococcal polysaccharide (SSS-III) were assessed for F(1), F(2), and backcross progeny derived from crosses between high responding BALB/cAnN (B) and low responding CBA/HN (C) mice. The results obtained confirmed our original hypothesis, namely, that a major component, present on the X chromosome, governs the ability to respond to SSS-III in a decisive manner. Although all low responding C mice had low IgM levels, both intermediate and high responders had high IgM levels of the same magnitude. Treatment with bacterial lipopolysaccharides (LPS) resulted in a significant increase in the IgM levels of low responding C mice. While the IgM levels attained were similar to those of high responding B mice, not given LPS, no antibody specific for LPS appeared to be produced. These findings suggest that C mice are unable to make an IgM antibody response to SSS-III and other polysaccharide antigens, despite the fact that they possess the capacity to synthesize normal amounts of IgM immunoglobulin.

Animals↗

Graft-vs.-host reactions in reciprocal hybrid mice. I. Dissociation of T-cell activities in the mixed lymphocyte reaction and two graft-vs.-host assays.

Spleen cells from BALB/c and C57BL/6 mice were tested for their reactivity against reciprocal hybrid tissues ((BALB/c x C57BL/6) F(1) and (C57BL/6 x BALB/c) F(1)) in three assay systems: the mixed lymphocyte reaction (MLR); the Simonsen spleen-weight graft-vs.-host (GVH) assay; and a GVH mortality assay. It was shown that both F(1)'s serve as equally effective stimulators of parental cells in the MLR. In the spleen-weight assay, BALB/c and C57BL/6 cells were equally active in a given host, but greater splenomegaly was observed in (BALB/c x C57BL/6) F(1) hosts regardless of the donor strain. By contrast, BALB/c cells were much less lethal than C57BL/6 cells in (BALB/c x C57BL/6) F(1) hosts than in (C57BL/6 x BALB/c) F(1) hosts, and to a lesser degree C57BL/6 cells were less lethal than BALB/c cells in (C57BL/6 x BALB/c) F(1) hosts. The possibility that modifying substances may differentially alter reactivity of parental lymphocytes and that considerations other than genotype determine the outcome of a GVH reaction are discussed in detail.

Animals↗

Synergy among lymphoid cells mediating the graft-versus-host response. V. Derivation by migration in lethally irradiated recipients of two interacting subpopulations of thymus-derived cells from normal spleen.

Spleen cells from normal adult mice were injected into lethally irradiated adult syngeneic recipients. 24 h later, cell suspensions were prepared from the recipients' spleens or peripheral lymph nodes and tested either alone or combined for their capacity to elicit graft-versus-host (GVH) reactions in neonatal F(1) recipients, using the Simonsen spleen weight assay. Either the lymph node-seeking subpopulation or the spleen-seeking subpopulation alone was markedly deficient in its ability to provide a GVH reaction when compared with the normal population from which it was derived. However, an appropriate mixture of the two had a reactivity characteristic of the parent population. Both subpopulations were sensitive to treatment with anti-theta antibody and complement in vitro. These results provide a convincing demonstration of the functional heterogeneity within the pool of thymus-derived cells present in a single normal lymphoid tissue. They strongly suggest that the normal expression of GVH reactivity of such a tissue involves an interaction among distinct subpopulations of thymus-derived cells.

Animals↗