ENZYMATICALLY PRODUCED SUBUNITS OF PROTEINS FORMED BY PLASMA CELLS IN MICE : II. β2A-MYELOMA PROTEIN AND BENCE JONES PROTEIN

The relationship of Bence Jones protein (mol wt = 45,000) to a β2A-myeloma protein (mol wt = 160,000) formed by the same mouse plasma cell tumor (MPC-2) was investigated. The β2A-myeloma protein was split by treatment with papain and cysteine into fragments (S20,w = 3.7S), similar in size to the Bence Jones protein (S20,w = 3.6S). Two types of fragments with distinct antigenic groupings designated S and F, were present in the MPC-2 myeloma protein digest. These were partially separated by DEAE-cellulose chromatography. The Bence Jones protein was found to share antigenic determinants with S fragments from the MPC-2 β2A-myeloma protein and with S fragments from γ-globulins. Physicochemical observations indicated, however, that the Bence Jones protein was not identical to the globulin fragments produced by treatment with papain and cysteine. Comparison of the S and F fragments from β2A- and γ-globulins revealed that the antigenic features shared by the various globulins derived from plasma cells (γ- and β2A-myeloma proteins, the range of normal γ-globulins) are largely properties of the S fragments, whereas the distinctive antigenic differences between the γ- and β2A-myeloma proteins were properties which appeared in the F fragments of the molecules

PERSISTENCE OF IMMUNOGENICITY OF ANTIGEN AFTER UPTAKE BY MACROPHAGES

Peritoneal macrophages were cultured for several hours after uptake of 131I-hemocyanin. The cells degraded most of the 131I-labeled protein within 2–5 hr. Their ability to prime lymphocytes of syngeneic mice for a secondary immune challenge remained unchanged for long periods of time despite the loss of more than 90% of the original content of antigen. The persistence of immunogenicity was associated with a small percentage of antigen retained by the cell in a form which was protected from rapid breakdown and elimination

Social Policy and Cultural Services: A Study of Scottish Border Museums as Implementers of Social Inclusion

This article examines the findings of an exploratory case study based on local authority museums in the Scottish Borders to assess the impact of social inclusion policies from the Scottish Parliament. Taken from museum curators’ perspectives, the findings suggest that social inclusion policies have not filtered through the system to reach the curators due to unclear government policy and confusion regarding terminology, strategy and guidelines. Curators found it difficult to engage with social inclusion discourse, despite employing socially inclusive actions in everyday practice. The relationship between the local community and museum was seen to be unique and multi-layered, with a perceived dimension of community ownership, which has implications for social policy on central, local and individual levels

EFFECTS OF LOW-DOSE-GAMMA RAYS ON THE IMMUNE SYSTEM OF DIFFERENT ANIMAL MODELS OF DISEASE

We reviewed the beneficial or harmful effects of low-dose ionizing radiation on several diseases based on a search of the literature. The attenuation of autoimmune manifestations in animal disease models irradiated with low-dose γ-rays was previously reported by several research groups, whereas the exacerbation of allergic manifestations was described by others. Based on a detailed examination of the literature, we divided animal disease models into two groups: one group consisting of collagen-induced arthritis (CIA), experimental encephalomyelitis (EAE), and systemic lupus erythematosus, the pathologies of which were attenuated by low-dose irradiation, and another group consisting of atopic dermatitis, asthma, and Hashimoto’s thyroiditis, the pathologies of which were exacerbated by low-dose irradiation. The same biological indicators, such as cytokine levels and Tcell subpopulations, were examined in these studies. Low-dose irradiation reduced interferon (IFN)-gamma (γ) and interleukin (IL)-6 levels and increased IL-5 levels and the percentage of CD4+CD25+Foxp3+Treg cells in almost all immunological disease cases examined. Variations in these biological indicators were attributed to the attenuation or exacerbation of the disease’s manifestation. We concluded that autoimmune diseases caused by autoantibodies were attenuated by low-dose irradiation, whereas diseases caused by antibodies against external antigens, such as atopic dermatitis, were exacerbated

Incomplete Cd8+ T Lymphocyte Differentiation as a Mechanism for Subdominant Cytotoxic T Lymphocyte Responses to a Viral Antigen

CD8+ cytotoxic T lymphocytes (CTLs) recognize antigen in the context of major histocompatibility complex (MHC) class I molecules. Class I epitopes have been classified as dominant or subdominant depending on the magnitude of the CTL response to the epitope. In this report, we have examined the in vitro memory CTL response of H-2d haplotype murine CD8+ T lymphocytes specific for a dominant and subdominant epitope of influenza hemagglutinin using activation marker expression and staining with soluble tetrameric MHC–peptide complexes. Immune CD8+ T lymphocytes specific for the dominant HA204-210 epitope give rise to CTL effectors that display activation markers, stain with the HA204 tetramer, and exhibit effector functions (i.e., cytolytic activity and cytokine synthesis). In contrast, stimulation of memory CD8+ T lymphocytes directed to the subdominant HA210-219 epitope results in the generation of a large population of activated CD8+ T cells that exhibit weak cytolytic activity and fail to stain with the HA210 tetramer. After additional rounds of restimulation with antigen, the HA210-219–specific subdominant CD8+ T lymphocytes give rise to daughter cells that acquire antigen-specific CTL effector activity and transition from a HA210 tetramer–negative to a tetramer-positive phenotype. These results suggest a novel mechanism to account for weak CD8+ CTL responses to subdominant epitopes at the level of CD8+ T lymphocyte differentiation into effector CTL. The implications of these findings for CD8+ T lymphocyte activation are discussed

Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture

The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants

The GPI-Phospholipase C of Trypanosoma brucei Is Nonessential But Influences Parasitemia in Mice

In the mammalian host, the cell surface of Trypanosoma brucei is protected by a variant surface glycoprotein that is anchored in the plasma membrane through covalent attachment of the COOH terminus to a glycosylphosphatidylinositol. The trypanosome also contains a phospholipase C (GPI-PLC) that cleaves this anchor and could thus potentially enable the trypanosome to shed the surface coat of VSG. Indeed, release of the surface VSG can be observed within a few minutes on lysis of trypanosomes in vitro. To investigate whether the ability to cleave the membrane anchor of the VSG is an essential function of the enzyme in vivo, a GPI-PLC null mutant trypanosome has been generated by targeted gene deletion. The mutant trypanosomes are fully viable; they can go through an entire life cycle and maintain a persistent infection in mice. Thus the GPI-PLC is not an essential activity and is not necessary for antigenic variation. However, mice infected with the mutant trypanosomes have a reduced parasitemia and survive longer than those infected with control trypanosomes. This phenotype is partially alleviated when the null mutant is modified to express low levels of GPI-PLC

Distinction of the memory B cell response to cognate antigen versus bystander inflammatory signals

The hypothesis that bystander inflammatory signals promote memory B cell (BMEM) self-renewal and differentiation in an antigen-independent manner is critically evaluated herein. To comprehensively address this hypothesis, a detailed analysis is presented examining the response profiles of B-2 lineage B220+IgG+ BMEM toward cognate protein antigen in comparison to bystander inflammatory signals. After in vivo antigen encounter, quiescent BMEM clonally expand. Surprisingly, proliferating BMEM do not acquire germinal center (GC) B cell markers before generating daughter BMEM and differentiating into plasma cells or form structurally identifiable GCs. In striking contrast to cognate antigen, inflammatory stimuli, including Toll-like receptor agonists or bystander T cell activation, fail to induce even low levels of BMEM proliferation or differentiation in vivo. Under the extreme conditions of adjuvanted protein vaccination or acute viral infection, no detectable bystander proliferation or differentiation of BMEM occurred. The absence of a BMEM response to nonspecific inflammatory signals clearly shows that BMEM proliferation and differentiation is a process tightly controlled by the availability of cognate antigen