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Rapid induction of autoantibodies by endogenous ovarian antigens and activated T cells: implication in autoimmune disease pathogenesis and B cell tolerance.
J Immunol. 1996 May 01; 156(9):3535-40.JI

Abstract

Animals immunized with nuclear antigenic peptides produce autoantibodies to distant antigenic sites and neighboring Ags within a multimolecular complex. This has led to the hypothesis that induction of autoantibodies in systemic autoimmune diseases might be triggered by a T cell epitope. We have investigated the T to B epitope spreading phenomenon based on the murine autoimmune oophoritis model. Mice immunized with a ZP3 T cell peptide spontaneously produced amplified autoantibodies (amAb) against linear ZP3 B cell epitopes outside the peptide immunogen. Each ZP3 B cell peptide, chimerized to a foreign promiscuous T cell epitope, elicited Ab to the peptide within the native ZP3 molecule. Mice with amAb often had no oophoritis; but more importantly, bilateral ovariectomy 1 day before ZP3 T epitope injection inhibited the induction of the amAb response, whereas ovariectomy 2 to 4 days after immunization was not inhibitory. Because endogenous ovarian Ag depletion before detectable ZP3 T cell response (day 5) and oophoritis (day 7) failed to prevent the amAb response, the autoantibodies are likely stimulated by endogenous ZP3 Ags present outside the normal ovaries. AmAb, of only the IgG class, appeared on day 7; this was 2 to 3 days after detectable T cell response, and 5 to 6 days before A response to the T cell peptide immunogen. The rapid, class-switched amAb response indicates that B cells in female mice are not tolerant to self ovarian Ag and they may normally be primed by ZP3. As evidence for their pathogenic potentials, amAb were produced in response to oophoritogenic, nonovarian T cell peptides that mimic ZP3; moreover, an excellent correlation existed between amAb titers and fertility reduction.

Authors+Show Affiliations

Department of Pathology, University of Virginia, Charlottesville 22908, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8617983

Citation

Lou, Y H., et al. "Rapid Induction of Autoantibodies By Endogenous Ovarian Antigens and Activated T Cells: Implication in Autoimmune Disease Pathogenesis and B Cell Tolerance." Journal of Immunology (Baltimore, Md. : 1950), vol. 156, no. 9, 1996, pp. 3535-40.
Lou YH, McElveen MF, Garza KM, et al. Rapid induction of autoantibodies by endogenous ovarian antigens and activated T cells: implication in autoimmune disease pathogenesis and B cell tolerance. J Immunol. 1996;156(9):3535-40.
Lou, Y. H., McElveen, M. F., Garza, K. M., & Tung, K. S. (1996). Rapid induction of autoantibodies by endogenous ovarian antigens and activated T cells: implication in autoimmune disease pathogenesis and B cell tolerance. Journal of Immunology (Baltimore, Md. : 1950), 156(9), 3535-40.
Lou YH, et al. Rapid Induction of Autoantibodies By Endogenous Ovarian Antigens and Activated T Cells: Implication in Autoimmune Disease Pathogenesis and B Cell Tolerance. J Immunol. 1996 May 1;156(9):3535-40. PubMed PMID: 8617983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid induction of autoantibodies by endogenous ovarian antigens and activated T cells: implication in autoimmune disease pathogenesis and B cell tolerance. AU - Lou,Y H, AU - McElveen,M F, AU - Garza,K M, AU - Tung,K S, PY - 1996/5/1/pubmed PY - 1996/5/1/medline PY - 1996/5/1/entrez SP - 3535 EP - 40 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 156 IS - 9 N2 - Animals immunized with nuclear antigenic peptides produce autoantibodies to distant antigenic sites and neighboring Ags within a multimolecular complex. This has led to the hypothesis that induction of autoantibodies in systemic autoimmune diseases might be triggered by a T cell epitope. We have investigated the T to B epitope spreading phenomenon based on the murine autoimmune oophoritis model. Mice immunized with a ZP3 T cell peptide spontaneously produced amplified autoantibodies (amAb) against linear ZP3 B cell epitopes outside the peptide immunogen. Each ZP3 B cell peptide, chimerized to a foreign promiscuous T cell epitope, elicited Ab to the peptide within the native ZP3 molecule. Mice with amAb often had no oophoritis; but more importantly, bilateral ovariectomy 1 day before ZP3 T epitope injection inhibited the induction of the amAb response, whereas ovariectomy 2 to 4 days after immunization was not inhibitory. Because endogenous ovarian Ag depletion before detectable ZP3 T cell response (day 5) and oophoritis (day 7) failed to prevent the amAb response, the autoantibodies are likely stimulated by endogenous ZP3 Ags present outside the normal ovaries. AmAb, of only the IgG class, appeared on day 7; this was 2 to 3 days after detectable T cell response, and 5 to 6 days before A response to the T cell peptide immunogen. The rapid, class-switched amAb response indicates that B cells in female mice are not tolerant to self ovarian Ag and they may normally be primed by ZP3. As evidence for their pathogenic potentials, amAb were produced in response to oophoritogenic, nonovarian T cell peptides that mimic ZP3; moreover, an excellent correlation existed between amAb titers and fertility reduction. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8617983/Rapid_induction_of_autoantibodies_by_endogenous_ovarian_antigens_and_activated_T_cells:_implication_in_autoimmune_disease_pathogenesis_and_B_cell_tolerance_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=8617983 DB - PRIME DP - Unbound Medicine ER -