Induction of Tolerance to an IgG Autoantibody

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Sep 1

PMID 1518867

Citations 24

Authors

D Offen

L Spatz

H Escowitz

S Factor

B Diamond

Affiliations

Soon will be listed here.

Abstract

Nonautoimmune mice transgenic for the heavy chain of an IgG2b anti-double-stranded-DNA antibody express the transgene in lymphoid organs and display partial allelic exclusion of this gamma 2b transgene. The spleens of these mice are characterized by marked B-cell depletion. Although there are B cells in these mice that express the transgene and recognize double-stranded DNA, they are anergic in vivo. Recovery from the state of anergy occurs in vitro after lipopolysaccharide stimulation. Thus this transgenic model demonstrates the induction of self tolerance to an IgG autoantibody.

Citing Articles

Hormonal milieu at time of B cell activation controls duration of autoantibody response.

Jeganathan V, Peeva E, Diamond B J Autoimmun. 2014; 53:46-54.

PMID: 24685232 PMC: 4388304. DOI: 10.1016/j.jaut.2014.02.007.

Antigen is required for maturation and activation of pathogenic anti-DNA antibodies and systemic inflammation.

Venkatesh J, Yoshifuji H, Kawabata D, Chinnasamy P, Stanevsky A, Grimaldi C J Immunol. 2011; 186(9):5304-12.

PMID: 21444762 PMC: 3192436. DOI: 10.4049/jimmunol.1000224.

Lessons from an anti-DNA autoantibody.

Cohen-Solal J, Diamond B Mol Immunol. 2011; 48(11):1328-31.

PMID: 21216012 PMC: 3104112. DOI: 10.1016/j.molimm.2010.12.003.

Differential roles of estrogen receptors α and β in control of B-cell maturation and selection.

Hill L, Jeganathan V, Chinnasamy P, Grimaldi C, Diamond B Mol Med. 2010; 17(3-4):211-20.

PMID: 21107497 PMC: 3060981. DOI: 10.2119/molmed.2010.00172.

Enhanced selection of high affinity DNA-reactive B cells following cyclophosphamide treatment in mice.

Kawabata D, Venkatesh J, Ramanujam M, Davidson A, Grimaldi C, Diamond B PLoS One. 2010; 5(1):e8418.

PMID: 20066044 PMC: 2798615. DOI: 10.1371/journal.pone.0008418.

References

Tucker P, Marcu K, Newell N, Richards J, Blattner F . Sequence of the cloned gene for the constant region of murine gamma 2b immunoglobulin heavy chain. Science. 1979; 206(4424):1303-6. DOI: 10.1126/science.117549. View

Shimizu A, Honjo T . Immunoglobulin class switching. Cell. 1984; 36(4):801-3. DOI: 10.1016/0092-8674(84)90029-1. View

Okamoto M, Murakami M, Shimizu A, Ozaki S, Tsubata T, Kumagai S . A transgenic model of autoimmune hemolytic anemia. J Exp Med. 1992; 175(1):71-9. PMC: 2119080. DOI: 10.1084/jem.175.1.71. View

Venkitaraman A, Williams G, Dariavach P, Neuberger M . The B-cell antigen receptor of the five immunoglobulin classes. Nature. 1991; 352(6338):777-81. DOI: 10.1038/352777a0. View

Radic M, Mascelli M, Erikson J, Shan H, Weigert M . Ig H and L chain contributions to autoimmune specificities. J Immunol. 1991; 146(1):176-82. View

Erikson J, Radic M, Camper S, Hardy R, Carmack C, Weigert M . Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice. Nature. 1991; 349(6307):331-4. DOI: 10.1038/349331a0. View

Hartley S, Crosbie J, Brink R, Kantor A, Basten A, Goodnow C . Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature. 1991; 353(6346):765-9. DOI: 10.1038/353765a0. View

Shefner R, Kleiner G, Turken A, Papazian L, Diamond B . A novel class of anti-DNA antibodies identified in BALB/c mice. J Exp Med. 1991; 173(2):287-96. PMC: 2118791. DOI: 10.1084/jem.173.2.287. View

Shlomchik M, Mascelli M, Shan H, Radic M, Pisetsky D, Marshak-Rothstein A . Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990; 171(1):265-92. PMC: 2187662. DOI: 10.1084/jem.171.1.265. View

10.

Tsang H, Pinkert C, Hagman J, Lostrum M, Brinster R, STORB U . Cloning of a gamma 2b gene encoding anti-Pseudomonas aeruginosa H chains and its introduction into the germ line of mice. J Immunol. 1988; 141(1):308-14. View

11.

Eilat D, Webster D, Rees A . V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice. J Immunol. 1988; 141(5):1745-53. View

12.

DeFranco A, Page D, Blum J, Gold M . Signal transduction by the antigen receptor of B lymphocytes. Cold Spring Harb Symp Quant Biol. 1989; 54 Pt 2:733-40. DOI: 10.1101/sqb.1989.054.01.086. View

13.

Scott D, Ales-Martinez J, Chace J, LoCascio N, Silver L, Warner G . Models of B-cell unresponsiveness. Cold Spring Harb Symp Quant Biol. 1989; 54 Pt 2:899-905. DOI: 10.1101/sqb.1989.054.01.105. View

14.

Nemazee D, Burki K . Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature. 1989; 337(6207):562-6. DOI: 10.1038/337562a0. View

15.

Jenkins M, Schwartz R . Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987; 165(2):302-19. PMC: 2188516. DOI: 10.1084/jem.165.2.302. View

16.

STORB U, Engler P, Manz J, Gollahon K, Denis K, Lo D . Expression of immunoglobulin genes in transgenic mice and transfected cells. Ann N Y Acad Sci. 1988; 546:51-6. DOI: 10.1111/j.1749-6632.1988.tb21618.x. View

17.

Yamamura K, Kudo A, Ebihara T, Kamino K, Araki K, KUMAHARA Y . Cell-type-specific and regulated expression of a human gamma 1 heavy-chain immunoglobulin gene in transgenic mice. Proc Natl Acad Sci U S A. 1986; 83(7):2152-6. PMC: 323249. DOI: 10.1073/pnas.83.7.2152. View

18.

Trepicchio Jr W, Barrett K . Eleven MRL-lpr/lpr anti-DNA autoantibodies are encoded by genes from four VH gene families: a potentially biased usage of VH genes. J Immunol. 1987; 138(7):2323-31. View

19.

STORB U . Transgenic mice with immunoglobulin genes. Annu Rev Immunol. 1987; 5:151-74. DOI: 10.1146/annurev.iy.05.040187.001055. View

20.

Behar S, Scharff M . Somatic diversification of the S107 (T15) VH11 germ-line gene that encodes the heavy-chain variable region of antibodies to double-stranded DNA in (NZB x NZW)F1 mice. Proc Natl Acad Sci U S A. 1988; 85(11):3970-4. PMC: 280342. DOI: 10.1073/pnas.85.11.3970. View