The Fine Specificity of Monoclonal Anti-DNA Antibodies Induced in Normal Mice by Immunization with Bacterial DNA

Pyun, Elise; Pisetsky, David S.; Gilkeson, Gary S.

doi:10.1006/jaut.1993.1002

Cited by 12 publications

(6 citation statements)

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“…Thus, sera from patients with lupus generally react with DNA independent of species origin as well as base composition [15, 35]. This finding suggests predominant binding to a conserved antigenic determinant, with backbone phosphates most likely.…”

Section: Discussionmentioning

confidence: 99%

The effect of polyamines on the binding of anti-DNA antibodies from patients with SLE and normal human subjects

Wang

Stearns

et al. 2014

Clinical Immunology

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Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE). To elucidate specificity further, the effect of polyamines on the binding of anti-DNA antibodies from patients with lupus was tested by ELISA to calf thymus (CT) DNA; we also assessed the binding of plasmas of patients and normal human subjects (NHS) to Micrococcus luteus (MC) DNA. As these studies showed, spermine can dose-dependently inhibit SLE anti-DNA binding to CT DNA and can promote dissociation of preformed immune complexes. With MC DNA as antigen, spermine failed to inhibit the NHS anti-DNA binding. Studies using plasmas adsorbed to a CT DNA cellulose affinity indicated that SLE plasmas are mixtures of anti-DNA that differ in inhibition by spermine and binding to conserved and non-conserved determinants. Together, these studies demonstrate that spermine can influence the binding of anti-DNA autoantibodies and may contribute to the antigenicity of DNA.

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Section: Discussionmentioning

confidence: 99%

The effect of polyamines on the binding of anti-DNA antibodies from patients with SLE and normal human subjects

Wang

Stearns

et al. 2014

Clinical Immunology

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“…In the analysis of Ab V H CDR3, arginines were present in four Abs, but no induced anti-DNA Abs contained more than one arginine in CDR3 or an arginine at position 100 or 100a. These anti-DNA Abs from normal mice displayed a broad range of reactivity with polynucleotides, cardiolipin, and lupus-associated autoantigens (Sm, Ro, and La) (38). Marion et al (35) described a panel of six anti-DNA Abs (four IgG and two IgM) derived from a single BALB/c mouse following immunization with a DNA binding peptide (Fus 1) in complex with native mammalian DNA.…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of the Autoantibody Response in Peptide-Induced Autoimmunity

Putterman

Deocharan

Diamond

2000

The Journal of Immunology

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Immunization of nonautoimmune BALB/c mice with multimeric DWEYSVWLSN, a peptide mimotope of DNA, induces anti-DNA and other lupus-associated Abs. To further investigate the pathogenesis of the autoantibody response induced by peptide immunization, we generated hybridomas from peptide-immunized mice that bound peptide, dsDNA, cardiolipin, Sm/ribonucleoprotein (RNP), or some combination of these Ags. Analysis of 24 IgM Abs led to the identification of three groups of Abs: 1) Abs reactive with peptide alone, 2) anti-peptide Abs cross-reactive with one or more autoantigens, and 3) autoantibodies that do not bind to peptide. The gene families and particular VH-VL combinations used in those hybridomas binding DNA were similar to those used in the anti-DNA response in spontaneous murine lupus. Another similarity to the spontaneous anti-DNA response was the generation of arginines in the complementarity-determining region-3 of DNA-binding hybridomas. Interestingly, one Ab had the VH-VL combination present in the original R4A anti-DNA Ab used to select the DWEYSVWLSN peptide from a phage display library. Many of the heavy and light chains displayed evidence of somatic mutation, suggesting that they were made by Ag-activated B cells. Analysis of the Ab repertoire in peptide-induced autoimmunity may provide insights into the generation of anti-DNA Abs following exposure to foreign Ag. Furthermore, the recovery of an Ab with the heavy and light chain combination of the Ab originally used to isolate the immunizing peptide confirms the utility of phage display peptide libraries in generating true molecular mimics.

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“…The respective antibodies share common immunochemical and structural features [5] and only some of them have peculiar properties that increase their potential to be pathogenic [6][7][8]. In contrast, bacterial DNA can induce anti-DNA antibodies by injection [9] and native mammalian DNA becomes antigenic when complexed with charged proteins such as histones [10]. Even histones acquire immunostimulating properties when linked to nucleic acids.…”

Section: Introductionmentioning

confidence: 99%