Intrastrain recurrent idiotypes among anti‐DNA antibodies of (NZB X NZW)F<sub>1</sub> hybrid mice

Tron, François; Guern, Christian Le; Cazenave, Pierre‐André; Bach, Jean‐François

doi:10.1002/eji.1830120911

Cited by 36 publications

(13 citation statements)

References 22 publications

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“…Evidence has been presented elsewhere for the anti-Id specificity of the NZB and A/J mouse antisera prepared against F227 mAb (7). The data in Table 2 provide similar evidence for the rabbit antiserum directed against PME77 mAb.…”

supporting

confidence: 73%

“…Two of them were prepared in mice (NZB and A/J) against the F227 anti-DNA mAb. These sera detected different idiotopes on the F227 molecules (7). None of these idiotopes was present on the nine other 'purified anti-ds DNA mAb.…”

Section: Discussionmentioning

confidence: 91%

“…Anti-Id antisera were prepared against F227 and PME77 anti-DNA mAb, which were obtained in two separate fusion experiments. The production and the characterization of NZB and A/J mouse antiId antisera against purified F227 mAb have been described (7). Briefly, anti-Id antisera prepared in NZB and A/J mice were shown to recognize different idiotopes of F227 mAb.…”

mentioning

confidence: 99%

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Murine monoclonal anti-DNA antibodies with an absolute specificity for DNA have a large amount of idiotypic diversity.

Tron¹,

Jacob²,

Bach³

1983

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

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The clonal heterogeneity of nine monoclonal antibodies with absolute specificities for deoxyribonucleic acid (DNA) was analyzed. These monoclonal anti-DNA antibodies were generated in three different fusion experiments using autoimmune (NZB x NZW)F1 mouse spleen cells. Isoelectric focusing analyses demonstrated different isoelectric points within the IgG2a and IgG2b subclasses. Three anti-idiotypic antisera were prepared (one in a rabbit and two in mice) against two monoclonal anti-DNA antibodies. These antisera detected idiotypic determinants uniquely associated with homologous hybridoma anti-DNA antibodies. Two of these idiotypes could be detected at low levels in the sera of (NZB x NZW)F1 mice. Anti-PME77 idiotypic antiserum had no effect in vitro on the total binding capacity of (NZB x NZW)F1 sera. Taken together these results demonstrate that, in (NZB x NZW)F1 mice, the anti-DNA antibody repertoire contains molecules that show similar antigen binding characteristics but are not structurally uniform.The autoimmune disease of (NZB x NZW)F1 (B/W) mice is characterized by the spontaneous development of hypergammaglobulinemia, hypocomplementemia, and glomerulonephritis, and it resembles human systemic lupus erythematosus. These mice produce a variety of autoantibodies, including antibodies directed against deoxyribonucleic acid (DNA), which are thought to play a major role in the pathogenesis of the disease (1).A detailed characterization of these autoantibodies is important to understanding the etiology of the disease and to studying autoimmune phenomena. More precisely, characterization would allow the definition of the homogeneous or, conversely, the heterogeneous nature of this antibody population, the determination of whether anti-DNA antibodies produced in murine systemic lupus erythematosus are identical to those produced by normal individuals, and the correlation of the presence of a particular family of anti-DNA antibodies with clinical manifestations.Hybridoma technology provides a unique opportunity to analyze the anti-DNA antibodies produced in vivo in autoimmune mice (B/W, MRL/1, BXSB). We recently reported the production from B/W spleen cells of anti-DNA monoclonal antibodies (mAb) whose antigenic specificities were demonstrated to be identical and directed against the B helical form of double-stranded DNA (ds DNA) (2,3).To investigate further the heterogeneity of the B cell clones producing anti-ds DNA antibodies, we studied the isoelectric focusing and idiotypic properties of nine anti-ds DNA 4). Cell Fusion. The hybridomas secreting anti-DNA antibodies were obtained after fusions between a nonsecreting myeloma line (P3x63-Ag8653) and B/W spleen cells. The selection of hybrids producing anti-DNA antibodies, cloning and subcloning of the lines, and characterization of the classes and subclasses of the antibodies were all described in detail previously (2).Purification of Anti-DNA mAb. Culture media were collected from the established hybridoma cell lines. Immunoglobulins (Ig) were prec...

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supporting

confidence: 73%

Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

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Murine monoclonal anti-DNA antibodies with an absolute specificity for DNA have a large amount of idiotypic diversity.

Tron¹,

Jacob²,

Bach³

1983

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

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“…Thus, the sharing of idiotypes amongst autoantibodies may offer clues to their origins. Earlier studies have demonstrated that there is much idiotype sharing amongst hybridoma-derived monoclonal anti-DNA antibody molecules found in the New Zealand black mice/New Zealand white mice (NZB/NZW) (19,20) and MRL lupus prone mice (21), and amongst human hybridomaderived anti-DNA autoantibodies (7). Further, anti-DNA autoantibody idiotype sharing has been shown amongst immunoglobulins in the serum of lupus patients (8).…”

Section: Discussionmentioning

confidence: 99%

Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients.

Isenberg¹,

Collins²

1985

J. Clin. Invest.

129

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Cross-reactive anti-DNA antibody idiotypes have been identified on tissue-bound immunoglobulins in a study of renal biopsies from 26 systemic lupus erythematosus (SLE) patients. 12 (46%) biopsies were shown to have one or both the idiotypes tested for by anti-idiotypic reagents. The idiotypes were identified in the glomerular basement membrane, the mesangial cell cytoplasm, and in focal tuft proliferations. In contrast, in none of 24 immunoglobulin-positive disease control biopsies could either idiotype be demonstrated. Blocking studies in two patients indicated that the idiotypes were on anti-DNA antibodies. These findings indicate that some tissue-bound autoantibodies are derived from related families of high-frequency germ line genes that are expressed in SLE patients. The potential role of anti-idiotypic therapy in SLE is discussed.

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“…This is significant in light of numerous studies which suggest that responses dominated by the expression of CRIs are particularly susceptible to idiotypic regulation. A majority of anti-DNA antibodies produced by lupusprone MRL-lprflpr and (New Zealand black x New Zealand white)F1 ([NZB x NZW]FI) mice express a CRI (16)(17)(18)(19)(20), as do the anti-DNA antibodies present in many humans with systemic lupus erythematosus (SLE) (21,22). CRIs have been identified on a high proportion of autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis (23) and in the sera of patients with myasthenia gravis (24)(25)(26)(27).…”

Section: Idiotypic Regulation Of the Immune Systemmentioning

confidence: 99%

Untitled

1986

Arthritis & Rheumatism

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Intrastrain recurrent idiotypes among anti‐DNA antibodies of (NZB X NZW)F₁ hybrid mice

Cited by 36 publications

References 22 publications

Murine monoclonal anti-DNA antibodies with an absolute specificity for DNA have a large amount of idiotypic diversity.

Murine monoclonal anti-DNA antibodies with an absolute specificity for DNA have a large amount of idiotypic diversity.

Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients.

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Intrastrain recurrent idiotypes among anti‐DNA antibodies of (NZB X NZW)F1 hybrid mice

Cited by 36 publications

References 22 publications

Murine monoclonal anti-DNA antibodies with an absolute specificity for DNA have a large amount of idiotypic diversity.

Murine monoclonal anti-DNA antibodies with an absolute specificity for DNA have a large amount of idiotypic diversity.

Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients.

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Intrastrain recurrent idiotypes among anti‐DNA antibodies of (NZB X NZW)F₁ hybrid mice