[en] BALB/c mice neonatally injected with semiallogeneic (C57BL/6 x BALB/c) F1 spleen cells become tolerant to C57BL/6 alloantigens and exhibit chimaerism due to persistence of F1 lymphocytes. Such mouse chimaeras develop an autoimmune (lupus-like) disease characterised by hypergammaglobulinaemia with production of autoantibodies against DNA, Sm antigen and other self-antigens characteristic of SLE in addition to circulating immune complexes and glomerular deposition of immunoglobulins. We have studied the autoimmune response by analysing the isoelectric focusing (IEF)+ patterns (spectrotypes) of anti-ss and anti-dsDNA antibodies produced by these animals. The results show that the anti-DNA response is remarkably restricted, only a very small number of lymphoid cell clones responding in the majority of animals. The behaviour of these clones has been followed during the development of the autoimmune response by analysis of their individual IEF patterns (clonotypes). The first appearance of clones secreting anti-DNA autoantibodies was observed in 3-4 week old mice. Changes in spectrotype occurred during the course of the response but they remained restricted to a very small number of clones in almost all the animals studied. Changes in clonotype consistent with somatic mutation in committed, anti-DNA-secreting clones were also observed. Helper T-lymphocytes of host origin are shown to be required for the development of an autoimmune response
Stott, D.; University of Glasgow > Bacteriology and Immunology
Merino, J.
Schurmans, Stéphane ; Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Institut de Biologie et de Médecine Moléculaire
Lambert, P. H.
Language :
English
Title :
Expression of anti-DNA clonotypes and the role of helper T-lymphocytes during the autoimmune response in mice tolerant to alloantigens
Hard R.C., Kullgren B. (1970) Etiology, pathogenesis and prevention of a fatal host-versus-graft syndrome in parent/F1 mouse chimeras. Am J Pathol 59:203-224.
Simpson E., Hopp O., Harrison S., Mosier M., Melief D., Cantor K.H. (1974) Immunological disease induced by injecting F1 lymphoid cells into certain parental strains. Immunology 27:989-1007.
Goldman M., Feng H., Engers H., Hochmann A., Louis J., Lambert P.-H. (1983) Autoimmunity and immune complex disease after neonatal induction of transplantation tolerance in mice. J Immunol 131:251-258.
Tateno M., Kondo N., Itoh T., Yoshiki T. (1985) Autoimmune disease and malignant lymphoma associated with host-versus-graft disease in mice. Clin Exp Immunol 62:535-544.
Merino J., Schurmans S., Luzuy S., Izui S., Vassalli P., Lambert P.-H. (1987) Autoimmune syndrome after induction of neonatal tolerance to alloantigens. Effects of in vivo treatment with anti-T cell subset monoclonal antibodies. J Immunol 139:1426-1431.
Luzuy S., Merino J., Engers H., Izui S., Lambert P.-H. (1986) Autoimmunity after induction of neonatal tolerance to alloantigens: role of B cell chimaerism and FI donor B cell activation. J. Immunol 136:4420-4426.
Williamson A.R. (1971) Antibody isoelectric spectra. Analysis of the heterogeneity of antibody molecules in serum by isoelectric focusing in gel and specific detection with hapten. Eur J Immunol 1:390-394.
Kreth H.W., Williamson A.R. (1973) The extent of diversity of anti-hapten antibodies in inbred mice: anti-NIP (4-hydroxy-5-iodo-3-nitro-phenacetyl) antibodies in CBA/H mice. Eur J Immunol 3:141-147.
Williamson A.R., Salaman M.R., Kreth H.W. (1973) Microheterogeneity and allomorphism of proteins. Annals N Y Acad Sci 209:210-224.
Stott D.I., McLearie J. (1986) lsoelectric focusing and reverse immunoblotting of autoantibodies against high molecular weight antigens. Immunol Invest 15:113-122.
Stott D.I., McLearie J., Neilson L. (1986) Analysis of the clonal origins of autoantibodies against thyrog-lobulin and DNA in autoimmune thyroiditis and systemic lupus erythematosus. Clin Exp Immunol 65:520-533.
Yoshida H., Yoshida M., Izui S., Lambert P.-H. (1985) Distinct clonotypes of anti-DNA antibodies in mice with lupus nephritis. J CIin Invest 76:685-694.
Sarmiento M., Glasebrook A.L., Fitch F.W. (1980) IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt2 antigen block T-cell mediated cytolysis in the absence of complement. J Immunol 125:2665-2672.
Maniatis T., Fritsch E.F., Sambrook J. Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor; 1982.
Conger J.D., Pike B.L., Nossal G.J.V. (1987) Clonal analysis of the anti-DNA repertoire of murine B-lymphocytes. Proc Nat Acad Sci USA 84:2931-2935.
Stott D.I., Feinstein A. (1973) Biosynthesis and assembly of IgM. Free thiol groups present on the intracell-ular subunits. Eur J Immunol 3:229-235.
Stott D.I. (1978) Biosynthesis and assembly of IgM. Free thiol groups present on cytoplasmic and membrane associated IgM. Immunol Commun 7:519-541.
Creighton T.E. (1980) Counting integral numbers of amino acid residues per polypeptide chain. Nature 284:487-489.
Flatmark T., Vesterberg O. (1966) On the heterogeneity of beef heart cytochrome C. IV. Isoelectric fractionation by electrolysis in a natural pH gradient. Acta Chem Scand 20:1497-1503.
Spencer E.M., King T.P. (1971) Isoelectric heterogeneity of bovine plasma albumin. J Biol Chem 246:201-208.
