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In vitroandin vivostudies identify IL-10 as a key cytokine that inhibits cell-mediated immunity and inflammation while promoting humoral responses. The present review summarizes our studies regarding the ability of B cells to secrete IL-10. When established lines are considered, the production of human IL-10 is restricted to mature B-cell lines and correlates with Epstein–Barr Virus (EBV) expression...
Bacterial production of recombinant Fab or Fv domains of antibodies is an important tool for analyzing structural correlates of antigen binding or idiotype expression. Bacterial products may be Fab or Fv molecules that assemble from separate chains in the periplasm or a single-chain Fv protein. This article describes properties and applications of a plasmid vector used for production of single-chain...
B-cell hyperactivity and production of pathogenic autoantibodies are the main immunological events in the pathogenesis of the human autoimmune disease systemic lupus erythematosus. One approach to studying the pathogenesis of this disease and to understanding how the autoantibody response is initiated and sustained has been to analyze the variable genes expressed by antibodies that have the hallmarks...
Anti-DNA antibodies are a major contributor to the pathogenesis associated with the autoimmune disease systemic lupus erythematosus in mice and human. The accumulation of a large body of structural information on autoimmune anti-DNA antibodies over the past several years, particularly from mice, has provided considerable insight into the structure, function, and biology of this important class of...
Interferons have effects on many facets of immune system development, maturation, and function. B cells are a target for the interferons, causing alterations in cell differentiation and gene expression. However, production of interferons by B cells has not been widely studied. In this review I will discuss the limited literature on B-cell interferon production. In addition I will describe results...
We analyzed the production and the roles of IL-6, IL-10, and IL-13 in B-lymphoid malignancies and in specific diseases with B-lymphocyte hyperactivity. Both IL-13 and IL-10 genes are expressed in B-cell lymphomas. However, their contribution to tumor progression is unclear. In certain lymphoproliferative disorders that develop in transplanted patients, IL-6 is produced by malignant cells and is a...
Biologically active granulocyte-colony stimulating factor (G-CSF) was released spontaneously in culture byin vivoactivated tonsillar B lymphocytes and, in particular, by the germinal center (GC) B-cell subset. In contrast, mantle zone B cells failed to produce the cytokine under any of the culture conditions tested. A CD40 monoclonal antibody (mAb), recombinant (r) IL4, and the combination of the...
Epstein–Barr Virus (EBV) effectively transforms B lymphocytes into long-term cell lines or tumors through the interaction of viral gene products and cellular proteins induced secondary to the virus infection. The latent membrane protein (LMP) gene, the EBV nuclear antigens (EBNAs) 1 and 2, and the origin of replication genes of the virus are the principal viral effectors of transformation. One of...
DNA is a structurally heterogeneous molecule that elicits antibody production in both normal and aberrant immunity. In the prototypic autoimmune disease systemic lupus erythematosus, anti-DNA antibodies occur prominently and are serological markers for diagnosis and prognosis. These antibodies target conserved sites on both single-stranded (ss) and double-stranded (ds) DNA from essentially all species...
We have identified monoclonal antibodies derived from MRL-lpr/lpr lupus-prone mice that produced nephritis after passive transfer to normal mice. Our present goal was to elucidate the structural and immunochemical features of nephritogenic Ig that facilitate immune deposition. For this purpose the antigen binding properties, capacity to form immune deposits, and nucleotide sequence of a genetically...
Although the origin of autoimmune antibodies to double-stranded DNA (dsDNA) is not known, the variable-region structures of such antibodies indicate that they are produced in response to antigen-selective stimulation. In accordance with this, results from experiments using artificial complexes of DNA and DNA-binding polypeptides for immunizations have indicated that DNA may induce these antibodies...
Individuals with systemic autoimmune diseases develop autoantibodies to nucleosome antigens. For many years, investigators have devoted much effort to precisely mapping epitopes on individual chromatin components. This approach, however, overlooks the existence of determinants that result from multimolecular interactions among nucleosome elements, such as DNA and histones. Anti-nucleosome antibodies...
Interleukin-5 was initially characterized in murine systems, where it was found to have B-lymphocyte proliferative and differentiative activity and to promote the growth of eosinophils. Recombinant production of human IL-5 was soon accomplished by using murine IL-5 cDNA to isolate the highly homologous human sequence. Although human IL-5 was also found to be an eosinophil-active growth factor, a significant...
Studies of anti-double-stranded (anti-ds)DNA antibodies have provided insights into how and why these antibodies arise in systemic lupus erythematosus. In this review we discuss the experimental approaches that have been used by our laboratory to study these autoantibodies. Structure/function analyses including site-directed mutagenesis have helped characterize the molecular genetics of anti-dsDNA...
Antigen selection of autoantibodies to DNA results in the use of limited sets of immunoglobulin heavy and light chains, characteristic VDJ and VJ joining regions, and recurrent patterns of somatic mutations. In the past, we have used site-directed mutagenesis to examine the roles of two recurrent features of anti-DNA antibodies: VHCDR3 arginine and somatic mutations to arginine. We observed that in...
Interleukin 12 (IL-12) is a heterodimeric protein produced by B cells, phagocytic cells, and other antigen-presenting cells. IL-12 was originally purified from the supernatant fluids of human EBV-transformed cell lines and later observed to be produced by the large majority of such cell lines, especially and at high levels from those derived from AIDS-associated lymphomas. However, phagocytic cells...
Two cytokines important in the regulation of B-cell function are tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). They act at different steps in B-cell differentiation and can be produced by the B cells themselves upon appropriate stimulation. Crosslinking of surface Ig and signaling through CD22 or CD40 lead to increased secretion of both cytokines. Neutralization of TNF-α or IL-6 biologic...
This paper describes anin vivoUV cross-linking protocol that is sensitive enough to detect DNA binding by sequence-specific transcription factors inDrosophilaembryos and tissue culture cells. The strength of this approach is that it provides a quantitative measure of DNA bindingin vivowith unambiguous identification of the factor involved in the binding. This assay often detects DNA binding properties...
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