Production of autoantibodies by human-human hybridomas.

Antiphospholipid syndrome (APIS) is characterized by thrombocytopenia, thromboembolic phenomena, and recurrent fetal loss, associated with anticardiolipin antibodies (ACA) and/or lupus anticoagulant. The syndrome may be primary or may be associated with other conditions such as systemic lupus erythematosus.We have previously shown the ability to induce APLS in naive mice following passive transfer of serum and monoclonal ACAs. Similarly we generated the secondary APLS in BALB/c mice following immunization with a pathogenic anti-DNA antibody. In the current study we report on the induction ofprimary APLS following immunization of BALB/c mice with a human monoclonal ACA (H-3). The mice developed high persistent titers of ACA. The APLS was characterized by prolonged activated partial thromboplastin time, low fecundity rate (21% vs. 48% of control immunized mice), high resorption index of fetuses (25% vs. 3%), and low weights of embryos and placentae.Our study points to the ability of inducing primary APLS in naive mice. The induction of various presentations of APLS by different ACA may explain the diversity of clinical manifestations seen in patients with APLS. (J. Clin. Incest. 1992.

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“…This model is analogous to our experiments on the induction of systemic lupus erythematosus (SLE) in mice using human anti-DNA antibody (9,10).…”

Section: Introductionmentioning

confidence: 81%

Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3).

Bakimer

Fishman²,

Blank³

et al. 1992

J. Clin. Invest.

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298

148

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“…The murine mAb 5G12 [IgG2a͞; 16͞6 Id ϩ anti-DNA (6)] and 103 [IgG2a͞; anti-(T,G)-A-L, (12)] were used. The human 16͞6 anti-DNA mAb (IgG1͞) was described (13,14). Control human IgG were purchased from Sigma.…”

Section: Methodsmentioning

confidence: 99%

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Waisman

Ruiz

Israeli

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Experimental systemic lupus erythematosus (SLE) can be induced in naive mice by immunization with a murine monoclonal anti-DNA antibody (mAb), 5G12, that bears a major idiotype designated 16͞6 Id. Strain-dependent differences were observed in the proliferative responses of lymph node cells of mice immunized with two peptides based on the sequences of the complementarity determining region (CDR) 1 and 3 of mAb 5G12. The capacity of the peptides to bind to major histocompatibility complex class II molecules correlated with the proliferative responses. Immunization of high responder strains with the CDR-based peptides led to production of autoantibodies and clinical manifestations characteristic to experimental SLE. The CDR-based peptides could prevent autoantibody production in neonatal mice that were immunized later either with the peptide or with the pathogenic autoantibody. Furthermore, the peptides inhibited specific proliferation of lymph node cells of mice immunized with the same peptide, with mAb 5G12 or with the human mAb anti-DNA, 16͞6 Id. Thus, the CDR-based peptides are potential candidates for therapy of SLE.

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“…The hypoxanthine phosphoribosyl transferase-deficient, hypoxanthine-aminopterine-thymidine (HAT) sensitive, IgG2K producer mutant cell Cell fusion. Fusion was performed according to the procedure described by Shoenfeld et al (9), with minor modifications as follows. Cells were mixed at ratios 1:1 and 5:1 (lymphoid cells/myeloma cells), co-pelleted by centrifugation (200 g, 10 min), and treated with 0.5 ml 44.4% polyethylene glycol 1450 (J. T. Baker Chemical Co., Phillipsburg, NY) in SFM.…”

Section: Methodsmentioning

confidence: 99%

“…The fusion of normal tonsillar lymphocytes with myeloma cells to produce human-human anti-DNA hybridomas should provide a unique system for comparison with hybridomas of SLE origin such as those that have been recently reported by Shoenfeld et al (9). This paper describes the production of monoclonal anti-DNA antibodies derived from normal tonsillar lymphocytes.…”

Section: Introductionmentioning

confidence: 98%

Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin.

Cairns¹,

Block²,

Bell³

1984

J. Clin. Invest.

128

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Abstract. Fusion of human myeloma cell line GM 4672 and tonsillar lymphoid cells from a normal donor resulted in 13 primary hybridomas, which produced IgM anti-single-stranded DNA (ssDNA) antibodies, as determined in enzyme-linked immunosorbent assay. Nine of these primary hybridomas have been cloned and a total of 34 clones were obtained. Supernatants of these cloned hybridomas were tested for binding to ssDNA, native DNA, RNA, low molecular weight supernatant DNA, polydeoxyguanylate-polydeoxycitidylate, polydeoxyadenylate-thymidylate sodium salt, and cardiolipin. Supernatants from all clones but one showed polyspecificity when reacting with the antigens tested. That the clones were true hybridomas rather than transformed lymphoid cells was evidenced by IgM anti-DNA antibody secretion, karyotype analysis, and HLA typing. These studies imply that immunoglobulin genes encoding for anti-DNA autoantibodies with a spectrum of nucleic acid specificities similar to systemic lupus erythematosus, exist among normal B lymphocytes. IntroductionThe presence of serum anti-DNA antibodies is characteristic

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Production of autoantibodies by human-human hybridomas.

Cited by 212 publications

References 8 publications

Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3).

Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3).

Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody

Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin.

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