Role of idiotype-anti-idiotype interactions in the induction of collagen-induced arthritis in rats. 2010

Liubov Beduleva, and Igor Menshikov
Department of Immunology, Udmurt State University, 1 Universitetskaya ul., Izhevsk 426011, Russian Federation. blv76@mail.ru

The mechanism of autoantibodies (rheumatoid factor (RF) and anti-collagen autoantibodies) induction in collagen-induced arthritis (CIA) is unknown. The study assessed the hypothesis that activation of autoantibody-producing clones is mediated by idiotype-anti-idiotype (IAI) interactions with lymphocytes on heterologous collagen. It was demonstrated that RF-containing serum of rats immunized with bovine collagen (BCII) in ELISA competes with BCII for binding to anti-BCII antibodies. Immunization of rats with Fc fragments of IgG caused not only an increase in RF levels, but also induction of antibodies to BCII and anti-collagen autoantibodies. Taken together, these facts suggest that activation of RF-producing lymphocytes in CIA model occurs through IAI interactions with anti-BCII lymphocytes. Three populations of antibodies were detected in the blood of arthritic rats: a population of antibodies reacting only with BCII, a population of antibodies reacting only with rat collagen (RCII) and a population of antibodies that can bind to both bovine and rat collagen. It was shown that RF in relation to anti-collagen autoantibodies act as anti-idiotype antibodies, and a comparative analysis of antibody production in arthritic and resistant rats demonstrated that the level of anti-collagen autoantibody production depends on the level of RF production. This suggests that RF and RF-producing lymphocytes are involved in regulation of anti-collagen autoreactive lymphocyte activity through an IAI interaction mechanism. A direct activation of autoreactive anti-RCII lymphocytes by BCII cannot be excluded, but it can be supposed that induction of anti-collagen autoreactive lymphocytes needs a signal generated in IAI interactions by RF-producing lymphocytes. This hypothesis is based on the data obtained, and not only explains the mechanism of autoreactive lymphocytes activation in the rat CIA model, but also indicates that the key regulatory element in the development of arthritis in animals is RF-producing lymphocytes. The results allow a new insight on the role of RF in the pathogenesis of rheumatoid arthritis and on seeking more effective therapeutic means.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007106 Immune Sera Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen. Antisera,Immune Serums,Sera, Immune,Serums, Immune
D007114 Immunization Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). Immunologic Stimulation,Immunostimulation,Sensitization, Immunologic,Variolation,Immunologic Sensitization,Immunological Stimulation,Sensitization, Immunological,Stimulation, Immunologic,Immunizations,Immunological Sensitization,Immunological Sensitizations,Immunological Stimulations,Sensitizations, Immunological,Stimulation, Immunological,Stimulations, Immunological,Variolations
D007130 Immunoglobulin Idiotypes Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains. Idiotypes, Immunoglobulin,Ig Idiotypes,Idiotype, Ig,Idiotype, Immunoglobulin,Idiotypes, Ig,Ig Idiotype,Immunoglobulin Idiotype
D007141 Immunoglobulin Fc Fragments Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN. Fc Fragment,Fc Fragments,Fc Immunoglobulin,Fc Immunoglobulins,Ig Fc Fragments,Immunoglobulin Fc Fragment,Immunoglobulins, Fc,Immunoglobulins, Fc Fragment,Fc Fragment Immunoglobulins,Fc Fragment, Immunoglobulin,Fc Fragments, Ig,Fc Fragments, Immunoglobulin,Fragment Immunoglobulins, Fc,Fragment, Fc,Fragments, Ig Fc,Immunoglobulin, Fc
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked

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