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J Clin Invest. 1990 January; 85(1): 86–92.
PMCID: PMC296390

Regulation of the anti-Sm autoantibody response in systemic lupus erythematosus mice by monoclonal anti-Sm antibodies.


The administration of certain monoclonal anti-Sm antibodies (2G7, 7.13) induced most MRL/lpr mice to become anti-Sm positive by 5 mo of age, although other anti-Sm monoclonals (Y2, Y12) suppressed the spontaneous response. Positive anti-Sm antibody enhancement occurred efficiently only in MRL/lpr mice and not in other systemic lupus erythematosus mice that have little spontaneous anti-Sm production. The enhancement by anti-Sm antibodies was specific for the anti-Sm response. The mechanism of the passive antibody enhancement was apparently not isotype- or idiotype-related. The fine specificity of the anti-Sm monoclonal antibody may be essential to its enhancing or suppressing effects, since both enhancing monoclonals recognized only the D Sm polypeptide, whereas both suppressing monoclonals saw the D and the B polypeptides. Furthermore, analysis of serial bleeds from unmanipulated MRL mice that developed anti-Sm positivity showed that the D specificity almost always appeared first. We hypothesize, therefore, that those animals in which an anti-Sm response is initiated by D-specific B-cell clones can become serologically positive with the aid of a positive feedback loop. In contrast, animals in which the initial specificity is for both B and D peptides would be prevented from developing a full anti-Sm response.

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Selected References

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  • Notman DD, Kurata N, Tan EM. Profiles of antinuclear antibodies in systemic rheumatic diseases. Ann Intern Med. 1975 Oct;83(4):464–469. [PubMed]
  • Eisenberg RA, Tan EM, Dixon FJ. Presence of anti-Sm reactivity in autoimmune mouse strains. J Exp Med. 1978 Feb 1;147(2):582–587. [PMC free article] [PubMed]
  • Lerner MR, Steitz JA. Snurps and scyrps. Cell. 1981 Aug;25(2):298–300. [PubMed]
  • Eisenberg RA, Dyer K, Craven SY, Fuller CR, Yount WJ. Subclass restriction and polyclonality of the systemic lupus erythematosus marker antibody anti-Sm. J Clin Invest. 1985 Apr;75(4):1270–1277. [PMC free article] [PubMed]
  • Eisenberg RA, Winfield JB, Cohen PL. Subclass restriction of anti-Sm antibodies in MRL mice. J Immunol. 1982 Nov;129(5):2146–2149. [PubMed]
  • Eisenberg RA, Craven SY, Warren RW, Cohen PL. Stochastic control of anti-Sm autoantibodies in MRL/Mp-lpr/lpr mice. J Clin Invest. 1987 Sep;80(3):691–697. [PMC free article] [PubMed]
  • Brennan FM, Williams DG, Bovill D, Stocks MR, Maini RN. Administration of monoclonal anti-Sm antibody prolongs the survival and renal function of MRL-lpr/lpr mice. Clin Exp Immunol. 1986 Jul;65(1):42–50. [PubMed]
  • Stocks MR, Williams DG, Maini RN. Differential induction of lupus associated antinuclear antibodies in MRL mice by monoclonal anti-Sm antibodies. Clin Exp Immunol. 1987 Mar;67(3):492–499. [PubMed]
  • Pisetsky DS, Hoch SO, Klatt CL, O'Donnell MA, Keene JD. Specificity and idiotypic analysis of a monoclonal anti-Sm antibody with anti-DNA activity. J Immunol. 1985 Dec;135(6):4080–4085. [PubMed]
  • Billings PB, Barton JR, Hoch SO. A murine monoclonal antibody recognizes the 13,000 molecular weight polypeptide of the Sm small nuclear ribonucleoprotein complex. J Immunol. 1985 Jul;135(1):428–432. [PubMed]
  • Lerner EA, Lerner MR, Janeway CA, Jr, Steitz JA. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc Natl Acad Sci U S A. 1981 May;78(5):2737–2741. [PubMed]
  • Pisetsky DS, Semper KF. Influence of assay conditions on ELISA determinations of anti-DNA antibodies. J Immunol Methods. 1984 Nov 30;74(2):217–227. [PubMed]
  • Mayus JL, Pisetsky DS. Expression of a highly conserved anti-DNA idiotype in normal and autoimmune mice. Clin Immunol Immunopathol. 1985 Mar;34(3):366–378. [PubMed]
  • Eisenberg RA, Klapper DG, Cohen PL. The polypeptide structure of the Sm and RNP nuclear antigens. Mol Immunol. 1983 Feb;20(2):187–195. [PubMed]
  • Fisher CL, Eisenberg RA, Cohen PL. Quantitation and IgG subclass distribution of antichromatin autoantibodies in SLE mice. Clin Immunol Immunopathol. 1988 Feb;46(2):205–213. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Thèze J, Löwy I, Seman M, Brézin C, Neauport-Sautes C, Fridman WH. Control of isotype expression by helper T-cell clones and suppressor cells. Ann Immunol (Paris) 1983 Jul-Aug;134D(1):55–61. [PubMed]
  • Pettersson I, Hinterberger M, Mimori T, Gottlieb E, Steitz JA. The structure of mammalian small nuclear ribonucleoproteins. Identification of multiple protein components reactive with anti-(U1)ribonucleoprotein and anti-Sm autoantibodies. J Biol Chem. 1984 May 10;259(9):5907–5914. [PubMed]
  • Habets WJ, Berden JH, Hoch SO, Van Venrooij WJ. Further characterization and subcellular localization of Sm and U1 ribonucleoprotein antigens. Eur J Immunol. 1985 Oct;15(10):992–997. [PubMed]
  • Mohn JF, Lambert RM, Bowman HS, Brason FW. Experimental production in man of autoantibodies with Rh specificity. Ann N Y Acad Sci. 1965 Jun 30;124(2):477–483. [PubMed]
  • Farkas AI, Medgyesi GA, Füst G, Miklós K, Gergely J. Immunogenicity of antigen complexed with antibody. I. Role of different isotypes. Immunology. 1982 Mar;45(3):483–492. [PubMed]
  • Coulie PG, Van Snick J. Enhancement of IgG anti-carrier responses by IgG2 anti-hapten antibodies in mice. Eur J Immunol. 1985 Aug;15(8):793–798. [PubMed]
  • Haughton G, Mäkelä O. Suppression or augmentation of the antihapten response in mice by antibodies of different specificities. J Exp Med. 1973 Jul 1;138(1):103–116. [PMC free article] [PubMed]
  • ter Borg EJ, Horst G, Hummel E, Jaarsma D, Limburg PC, Kallenberg CG. Sequential development of antibodies to specific Sm polypeptides in a patient with systemic lupus erythematosus: evidence for independent regulation of anti-double-stranded DNA and anti-Sm antibody production. Arthritis Rheum. 1988 Dec;31(12):1563–1567. [PubMed]
  • Cohen PL, Shores EW, Rapoport R, Caster S, Eisenberg RA, Pisetsky DS. Anti-Sm autoantibodies in MRL mice: analysis of precursor frequency. Cell Immunol. 1985 Dec;96(2):448–454. [PubMed]
  • Shores EW, Eisenberg RA, Cohen PL. Role of the Sm antigen in the generation of anti-Sm autoantibodies in the SLE-prone MRL mouse. J Immunol. 1986 May 15;136(10):3662–3667. [PubMed]
  • Shores EW, Pisetsky DS, Grudier J, Eisenberg RA, Cohen PL. Immunization with the Sm nuclear antigen induces anti-Sm antibodies in normal and MRL mice. Immunology. 1988 Nov;65(3):473–478. [PubMed]

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