Experimental systemic lupus erythematosus can be induced in naive mice of different strains using a human monoclonal antibody bearing the 16/6 idiotype and a murine anti-16/6 Id monoclonal antibody designated 1A3-2. Herein we report the isolation of a second anti-16/6 Id antibody, 3F7-8, from BALB/c mice afflicted with experimental SLE. In contrast to the previously reported (1A3-2) anti-16/6 Id monoclonal antibody, mAb 3F7-8 does not induce experimental SLE upon immunization. The variable heavy and light chains of both anti bodies were cloned and their sequences were determined. The VH of mAb 1A3-2 was found to express a germ line gene from the Q52 family, with a high homology to an anti-lysozyme antibody. The VH of monoclonal antibody 3F7-8 was found to express a 7183 germ line gene, showing over 95% homology with the VH of 12 anti-Sm antibodies isolated from MRL-1pr mice. Based on sequence homology to other known antibodies, we further demon strated that monoclonal antibodies 1A3-2 and 3F7-8 bind lysozyme and the Sm ribonu cleoproteins, respectively, in addition to their binding to the 16/6 Id.
Jerne NKTowards a network theory of the immune system. Annu Immunol (Paris) 1974; 125C: 435-441.
2.
Strosberg AD , Couraud PO, Schreiber A.Immunological studies of hormone receptors: a two-way approach. Immunol Today1981; 2: 75-79.
3.
Wassermann NH , Penn AS, Freimuth PIAnti-idiotypic route to anti-acetylcholine receptors antibodies and experimental Myasthenia gravis . Proc Natl Acad Sci USA1982; 79; 4810-4814.
4.
Islam MN, Pepper BM, Briones-Urbina R., Farid NRBiological activity of a anti-thyrotropin anti-idiotypic antibody . Eur J Immunol1983; 13: 57-63.
5.
Rajewsky K., Takemori T.Genetics, expression and function of idiotypes. Annu Rev Immunol1983; 1: 569-607.
6.
Elias D., Maron R., Cohen IR, Shechter Y.Mouse antibodies to insulin receptor developing spontaneously as anti-idiotypes . J Biol Chem1984; 259: 6416-6419.
7.
Shechter Y., Maron R., Elias D., Cohen IRAutoantibodies to insulin receptor spontaneously develop as anti-idiotypes in mice immunized with insulin. Science1982 ; 216: 542-545.
8.
Zanetti M., Rogers J., Katz DHInduction of autoantibodies to thyroglobulin by anti-idiotypic antibodies . J Immunol1984; 133: 240-243.
9.
Pisetsky DS, Hoch SO, Klatt CL, O'Donell MA, Keene JD. Specificity and idiotypic analysis of a monoclonal anti-Sm antibody with anti-DNA activity. J Immunol1985; 135: 4080-4085.
10.
Kaburaki J. , Stollar BDIdentification of human anti-DNA, anti-RNP, anti-Sm and anti-SS-A serum antibodies bearing the cross-reactive 16/6 Id . J Immunol1987; 139: 385-392.
11.
Migliorini P. , Ardman B., Kaburaki J., Schwartz RSParallel sets of autoantibodies in MRL-1pr/1pr mice. An anti-DNA, anti-SmRNP, anti-gp70 network. J Exp Med1987; 165: 483-499.
12.
Mendlovic S. , Brocke S., Shoenfeld Y., Ben-Bassat M., Meshorer A., Bakimer R., Mozes E.Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype. Proc Natl Acad Sci USA1988; 85: 2260-2264.
13.
Mendlovic S. , Fricke H., Shoenfeld Y., Mozes E.The role of anti-idiotypic antibodies in the induction of experimental systemic lupus erythematosus in mice. Eur J Immunol1989; 19: 729-734.
14.
Eshhar Z., Ofarim M., Waks T.Generation of hybridomas secreting murine reagenic antibodies of anti-DNP specificity. J Immunol1980; 124: 775-780.
15.
Siraganian RR, Fox PC, Berenstein EHMethods of enhancing the frequency of antigen-specific hybridomas. Methods Enzymol1983; 92: 17-26.
16.
Waisman A., Mendlovic S., Ruiz PJ, Zinger H., Meshorer A., Mozes E.The role of the 16/6 Id network in the induction and manifestations of systemic lupus erythematosus. Int Immunol1993; 5: 1293-1300.
17.
Dignam JD, Lebovitz RM, Roeder RDAccurate transcription initiation by RNA polymerase II in soluble extract from isolated mammalian nuclei. Nucleic Acids Res1983; 11: 1475-1489.
18.
Towbin H., Staehelin T., Gordon J.Electrophoretic transfer of protein from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA1979; 76: 4350-4354.
19.
Fricke H., Offen D., Mendlovic S., Shoenfeld Y., Bakimer R., Sperling J., Mozes E.Induction of experimental systemic lupus erythematosus in mice by immunization with a monoclonal anti-La autoantibody. Int Immunol1990; 2: 225-230.
20.
Sambrook J. , Fritsch EF, Maniatis T.Molecular Cloning. Cold Spring Harbor: New York, 1989.
21.
Orlandi R., Gussow DH, Jones PT, Winter G.Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proc Natl Acad Sci USA1989 ; 86: 3833-3837.
22.
Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S.Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature1980 ; 268: 676-683.
23.
Chothia C., Lesk AM, Levitt M., Amit AE, Mariazza RA, Phillips SE, Poljak RJThe predicted structure of immunoglobulin D1.3 and its comparison with the crystal structure. Science1986; 233: 755-758.
24.
Caton AJ, Stark SE, Kavaler J., Staudt LM, Schwartz D., Gerhard W.Many variable region genes are utilized in the antibody response of BALB/c mice to the influenza virus A/PR/8/34 hem-agglutinin. J Biol Chem1991; 147: 1675-1686.
25.
Jemmerson R. , Mueller C., Flaa D.Differences in heavy and light chain amino acid sequences affecting the specificity of antibodies for variants of cytochrome c. Unpublished Accession number L02500 (GenBank).
26.
Heinrich G. , Gram H., Kocher HP, Schrier MN, Ryffel B., Akbar A., Amlot PL, Janossy G.Characterization of a human T cell-specific chimeric antibody (CD7) with human constant and mouse variable regions. J Immunol1989; 143: 3589-3597.
27.
Lawler AM, Lin PS, Gearhart PJAdult B-cell repertoire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells. Proc Natl Acad Sci USA1987; 84: 2454-2458.
28.
Bloom DD, Davignon J-L.,Retter MW, Shlomchik MJ, Pisetsky DS, Cohen PL, Eisenberg RA, Clarke SHV region gene analysis of anti-S hybridomas from MRL/Mp-lpr/lpr mice . J Immunol1993; 150: 1591-1610.
29.
Tillman DM, Nainn-Tsyr J., Hill RJ, Marion TNBoth IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. J Exp Med176: 761-779.
30.
Tan ENAntinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol1989 ; 44: 93-151.
31.
Sthoeger ZM , Tartakovsky B., Bentwitch Z., Mozes E.Monoclonal anticardiolipin antibodies derived from mice with experimental lupus erythematosus: characterization and the induction of a secondary antiphospholipid syndrome. J Clin Immunol1993; 13: 127-138.
32.
Waisman A., Mozes E.Variable region sequences of autoantibodies from mice with experimental systemic lupus erythematosus. Eur J Immunol1993; 23: 1566-1573.
33.
Ast G., Goldblatt D., Waisman A., Sperling R., Mozes E., Sperling J.An autoantibody derived from mice with experimental systemic lupus erythematosus is directed against the essential splicing factor SF53/4-a possible role for large nuclear ribonucleoprotein particles in autoimmune disorders . Int Immunol1994; 6: 1097-1105.
34.
Brennan FM, Williams DG, Bovill D., Stocks MR, Maini RNAdministration of monoclonal anti-Sm antibody prolongs the survival and renal function of MRL-lpr/lpr mice. Clin Exp Immunol1986; 65: 42-50.
35.
Stocks MR, Williams DG, Maini RNDifferential induction of lupus associated antinuclear antibodies in MRL mice by monoclonal anti-Sm antibodies. Clin Exp Immunol1987; 67: 492-497.
36.
Eisenberg RA , Pisetsky DS, Craven SY, Grudier JP, O'Donnell MA, Cohen PLRegulation of the anti-Sm autoantibody response in systemic lupus erythematosus mice by monoclonal anti-Sm antibodies. J Exp Med1990; 85: 86-92.
37.
Brodeur PH, Osman GE, Mackle JJ, Lalor TMThe organization of the mouse Igh-V locus. Dispersion, interspersion and evolution of VH gene family clusters. J Exp Med1988; 168: 2261-2278.
38.
Kleinfield RW, Weigert MGInterspersion of the VHQ52 and VH7183 gene families in the NFS/N mouse. J Immunol1989; 142: 4483-4492.
39.
Monestier M. , Novick KE, Losman MJD-penicillamine- and Quinidine-induced antinuclear antibodies in A.SW (H-2s) mice: similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity. Eur J Immunol1994; 24: 723-730.
40.
Komori T., Minami Y., Sakato N., Sugiyama H., Biased usage of two restricted VH gene segments in V H replacements. Eur J Immunol1993; 23: 517-522.
41.
Paul E., Manheimer LA, Livneh A., Solomon A., Aronow C., Ghosslin C., Shefner R., Offen D., Pillinger M., Diamond B.Pathogenic anti-DNA antibodies in SLE: idiotypic families and genetic origins . Int Rev Immunol1990; 5: 295-313.
42.
Diamond B., Katz JB, Paul E., Aranow C., Lustgarten D., Scharff MDThe role of somatic mutation in the pathogenic anti-DNA response. Annu Rev Immunol1992; 10: 731-757.
43.
van Es JH, Aanstoot H., Gmelig Mfh, Derksen RH, Logtenberg T.A human systemic lupus erythematosus-related anticardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene. J Immunol1992; 149: 2234-2240.
44.
Marion TN, Bothwell AL, Briles DE, Janeway CJIgG anti-DNA autoantibodies within an individual autoimmune mouse are the products of clonal selection. J Immunol1989 ; 142: 4269-4274.
45.
Shlomchik M. , Mascelli M., Shan H., Rodic MZ, Pisetsky D., Marshak-Rothstein A., Weigert M.Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med1990; 171: 265-269.
46.
Kabat EA, Wu TT, Perry HM, Gottesman KS, Foeller K.Sequences of proteins of immunological interest. United States Department of Health and Human Services ( PHS , NIH): Bethesda, MD, 1991.
