A high dose of an idiotype generates high levels of Ab2s.

BACKGROUND Network perturbations have been reported in autoimmune processes which could cause polyclonal cell activation. MATERIALS AND METHODS Hyper-immunization was achieved by the injection of 3 mg of human monoclonal IgM DJ into BALB/c mice. Indirect ELISA was performed to detect induced antibody specificities. Competitive ELISAs were carried out on sera to detect the idiotypes expressed in first (Ab1) and second (Ab2) antibodies in sequence. RESULTS In the sera of hyper-immunized mice, the concentrations of Ab1 and Ab2 were respectively five and ten times higher than in the sera of normoimmunized mice. Polyclonal lymphocyte activation was demonstrated by an increase in antibodies specific for antigens (cytochrome C) not related to the immunizing antigen, elevated levels of IgM antibodies specific for the immunogen and elevated levels of Ab2s of the IgM isotype. CONCLUSION These findings are indicative of antigen-dependent network perturbation being a causative factor in polyclonal lymphocyte activation.

[1]  Z. Popovic,et al.  Changes in pools of autoantibodies and anti-bacterial antibodies in patients suffering from recurrent infections of the urinary tract and undergoing bacterial immunization treatment. , 2004, Immunology letters.

[2]  S. Burrows.  Cross-reactive recognition of viral and self-peptides by a "public" T cell receptor expressed by cytotoxic T lymphocytes expanded in multiple unrelated individuals. , 2004, Immunology letters.

[3]  Z. Popovic,et al.  Expression of Y7 Cross‐Reactive Idiotope on Human IgM Molecules , 2004, Immunological investigations.

[4]  Antonio Lanzavecchia,et al.  Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells , 2002, Science.

[5]  A. Tobar,et al.  Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. , 2002, The Journal of clinical investigation.

[6]  J. Elliott,et al.  Expansion of the Antigenic Repertoire of a Single T Cell Receptor upon T Cell Activation1 , 2001, The Journal of Immunology.

[7]  M. Croft,et al.  Functional cooperation between T helper cell determinants. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[8]  L. Frati,et al.  Cryptic epitopes on alpha-fetoprotein induce spontaneous immune responses in hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis patients. , 1999, Cancer research.

[9]  M. Croft,et al.  Activation of CD4 T cells by somatic transgenesis induces generalized immunity of uncommitted T cells and immunologic memory. , 1999, Journal of immunology.

[10]  L. Herzenberg,et al.  Innate and acquired humoral immunities to influenza virus are mediated by distinct arms of the immune system. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  B. Tsao,et al.  Evidence for multiple mechanisms of polyclonal T cell activation in murine lupus. , 1998, The Journal of clinical investigation.

[12]  P. Rogers,et al.  High antigen density and IL-2 are required for generation of CD4 effectors secreting Th1 rather than Th0 cytokines. , 1998, Journal of immunology.

[13]  K. Rajewsky,et al.  The Molecular Mechanism of B Cell Activation by toll-like Receptor Protein RP-105 , 1998, The Journal of experimental medicine.

[14]  A. Woodard,et al.  Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells , 1995, The Journal of experimental medicine.

[15]  A. Coutinho,et al.  The Network Theory: 21 Years Later , 1995, Scandinavian journal of immunology.

[16]  Y. Shoenfeld.  Idiotypic induction of autoimmunity: a new aspect of the idiotypic network , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  M. Segre,et al.  Behavior of the idiotypic network in conventional immune responses. III. Detection and enumeration of cells producing idiotypic and anti-idiotypic antibodies by a spot ELISA technique. , 1994, Cellular immunology.

[18]  H. Ikematsu,et al.  Structural analysis of the VH-D-JH segments of human polyreactive IgG mAb. Evidence for somatic selection. , 1993, Journal of immunology.

[19]  K. Garcia,et al.  Recognition of angiotensin II: antibodies at different levels of an idiotypic network are superimposable. , 1992, Science.

[20]  A S Perelson,et al.  Localized memories in idiotypic networks. , 1990, Journal of theoretical biology.

[21]  F. Varela,et al.  Dynamics of a class of immune networks. I. Global stability of idiotype interactions. , 1990, Journal of theoretical biology.

[22]  A. Perelson.  Immune Network Theory , 1989, Immunological reviews.

[23]  P Hogeweg,et al.  Idiotypic networks incorporating T-B cell co-operation. The conditions for percolation. , 1989, Journal of theoretical biology.

[24]  F. Varela,et al.  Evidence for a functional idiotypic network among natural antibodies in normal mice. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[25]  E. Voss,et al.  Quantitative analyses of immune network components. , 1989, Journal of immunology.

[26]  C. Bona,et al.  Regulatory Arms of the Immune Network , 1984, Immunological reviews.

[27]  A. Coutinho,et al.  From an Antigen‐Centered, Clonal Perspective of Immune Responses to an Organism‐Centered, Network Perspective of Autonomous Activity in a Self‐Referential Immune System , 1984, Immunological reviews.

[28]  K. Bottomly.  1984: All Idiotypes are Equal, But Some are More Equal Than Others , 1984, Immunological reviews.

[29]  J J Hopfield,et al.  Neural networks and physical systems with emergent collective computational abilities. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. E. Parks,et al.  Polyclonal B lymphocyte activation during Trypanosoma cruzi infection. , 1980, Journal of immunology.

[31]  G. Kelsoe,et al.  Reciprocal expansions of idiotypic and anti-idiotypic clones following antigen stimulation , 1979, Nature.

[32]  P. Diaz,et al.  BAL and serum IgG levels in healthy asymptomatic HIV-infected patients. , 2001, Chest.

[33]  M. Radulovic,et al.  Human monoclonal IgM DJ binds to ssDNA and human commensal bacteria. , 1999, Human antibodies.

[34]  S. Constant,et al.  Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. , 1997, Annual review of immunology.

[35]  Gérard Weisbuch,et al.  Window automata analysis of population dynamics in the immune system. , 1992 .

[36]  T. Odrljin,et al.  Immunochemical characterisation of a murine monoclonal anti-idiotypic antibody. , 1992, Journal of immunoassay.

[37]  Avidan U. Neumann,et al.  Window automata analysis of population dynamics in the immune system , 1992, Bulletin of mathematical biology.

[38]  F. Varela,et al.  Second generation immune networks. , 1991, Immunology today.

[39]  F T Vertosick,et al.  Immune network theory: a role for parallel distributed processing? , 1989, Immunology.

[40]  Pauline Hogeweg,et al.  Memory but no suppression in low-dimensional symmetric idiotypic networks , 1989, Bulletin of mathematical biology.

[41]  Jerne Nk.  Towards a network theory of the immune system. , 1974 .

[42]  N K Jerne,et al.  Towards a network theory of the immune system. , 1973, Annales d'immunologie.