V Gene Analysis of Anti-cardiolipin Antibodies from (NZW X BXSB) F1 Mice

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 1994 Jul 1

PMID 7959886

Citations 2

Authors

Y Kita

T Sumida

I Iwamoto

S Yoshida

T Koike

Affiliations

Soon will be listed here.

Abstract

In (NZW x BXSB) F1 (W/B F1) male mice, systemic lupus-like disease, thrombocytopenia and coronary vascular disease with myocardial infarction occur, due to the presence of platelet-associated antibodies, anti-platelet antibodies and anti-cardiolipin antibodies (aCL). We developed monoclonal aCL and analysed the specificity of aCL. In the W/B F1 mice, there are aCL with pathogenic properties, which have an IgG isotype and reveal a cofactor-dependent binding to CL, binding activity to platelets, and lupus anti-coagulant (LA) activity. Here, we analysed the usage of VH and V kappa genes of six aCL, including two pathogenic aCL, from W/B F1 mice, in an attempt to address the question of whether or not aCL with pathogenic properties use restricted Ig V genes. Sequence analysis of VH and V kappa genes of aCL showed that the pathogenic aCL had VHJ558 and V kappa 21 or V kappa 23 genes, whereas the other aCL without pathogenic features used mainly the 7183 VH family and the random V kappa gene group. However, two pathogenic aCL showed a 86.6% homology with the IgV region, each other, indicating that they were not closely related clones. Thus, these findings suggest the possibility that usage of Ig VH genes in pathogenic aCL is not random, but that there may exist a few epitopes of antigen recognized by the pathogenic aCL.

Citing Articles

Pathophysiology of the antiphospholipid antibody syndrome.

Willis R, Pierangeli S Auto Immun Highlights. 2015; 2(2):35-52.

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Antibody production in autoimmune BXSB mice. I. CD40L-expressing B cells need fewer signals for polyclonal antibody synthesis.

Blossom S, Gilbert K Clin Exp Immunol. 1999; 118(1):147-53.

PMID: 10540172 PMC: 1905385. DOI: 10.1046/j.1365-2249.1999.01032.x.

References

Sikder S, Akolkar P, Kaladas P, Morrison S, KABAT E . Sequences of variable regions of hybridoma antibodies to alpha (1----6) dextran in BALB/c and C57BL/6 mice. J Immunol. 1985; 135(6):4215-21. View

Meek K, Sanz I, Rathbun G, Nisonoff A, Capra J . Identity of the V kappa 10-Ars-A gene segments of the A/J and BALB/c strains. Proc Natl Acad Sci U S A. 1987; 84(17):6244-8. PMC: 299047. DOI: 10.1073/pnas.84.17.6244. View

Rajewsky K, Forster I, Cumano A . Evolutionary and somatic selection of the antibody repertoire in the mouse. Science. 1987; 238(4830):1088-94. DOI: 10.1126/science.3317826. View

Shlomchik M, Aucoin A, Pisetsky D, WEIGERT M . Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci U S A. 1987; 84(24):9150-4. PMC: 299710. DOI: 10.1073/pnas.84.24.9150. View

Oyaizu N, Yasumizu R, Nomura S, Yoshida H, Miyawaki S, Shibata Y . (NZW x BXSB)F1 mouse. A new animal model of idiopathic thrombocytopenic purpura. J Exp Med. 1988; 167(6):2017-22. PMC: 2189685. DOI: 10.1084/jem.167.6.2017. View

Rathbun G, Otani F, Milner E, Capra J, Tucker P . Molecular characterization of the A/J J558 family of heavy chain variable region gene segments. J Mol Biol. 1988; 202(3):383-95. DOI: 10.1016/0022-2836(88)90272-0. View

Forster I, Gu H, Rajewsky K . Germline antibody V regions as determinants of clonal persistence and malignant growth in the B cell compartment. EMBO J. 1988; 7(12):3693-703. PMC: 454942. DOI: 10.1002/j.1460-2075.1988.tb03251.x. 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

Ewulonu U, Nell L, Thomas J . VH and VL gene usage by murine IgG antibodies that bind autologous insulin. J Immunol. 1990; 144(8):3091-8. View

10.

McNeil H, Simpson R, Chesterman C, Krilis S . Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A. 1990; 87(11):4120-4. PMC: 54059. DOI: 10.1073/pnas.87.11.4120. View

11.

Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T . Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet. 1990; 336(8708):177-8. DOI: 10.1016/0140-6736(90)91697-9. View

12.

Van Es J, Gmelig Meyling F, van de Akker W, Aanstoot H, Derksen R, Logtenberg T . Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus. J Exp Med. 1991; 173(2):461-70. PMC: 2118793. DOI: 10.1084/jem.173.2.461. View

13.

Koike T, Matsuura E . What is the "true" antigen for anticardiolipin antibodies?. Lancet. 1991; 337(8742):671-2. DOI: 10.1016/0140-6736(91)92482-h. View

14.

McNeil H, Chesterman C, Krilis S . Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol. 1991; 49:193-280. DOI: 10.1016/s0065-2776(08)60777-4. View

15.

Taki S, Hirose S, Kinoshita K, Nishimura H, Shimamura T, Hamuro J . Somatically mutated IgG anti-DNA antibody clonally related to germ-line encoded IgM anti-DNA antibody. Eur J Immunol. 1992; 22(4):987-92. DOI: 10.1002/eji.1830220417. View

16.

Hashimoto Y, Kawamura M, Ichikawa K, Suzuki T, Sumida T, Yoshida S . Anticardiolipin antibodies in NZW x BXSB F1 mice. A model of antiphospholipid syndrome. J Immunol. 1992; 149(3):1063-8. View

17.

Van Es J, Aanstoot H, Gmelig-Meyling F, Derksen R, Logtenberg T . A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene. J Immunol. 1992; 149(6):2234-40. View

18.

Kita Y, Sumida T, Ichikawa K, Maeda T, Yonaha F, Iwamoto I . V gene analysis of anticardiolipin antibodies from MRL-lpr/lpr mice. J Immunol. 1993; 151(2):849-56. View

19.

Bothwell A, Paskind M, Reth M, Rajewsky K, Baltimore D . Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region. Cell. 1981; 24(3):625-37. DOI: 10.1016/0092-8674(81)90089-1. View

20.

Hang L, Izui S, Dixon F . (NZW x BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction. J Exp Med. 1981; 154(1):216-21. PMC: 2186385. DOI: 10.1084/jem.154.1.216. View