Surface antigen specificity of cold‐reactive IgM antilymphocyte antibodies in systemic lupus erythematosus

Yamada, Akira; Shaw, Melody; Winfield, John B.

doi:10.1002/art.1780280108

Cited by 24 publications

(12 citation statements)

References 28 publications

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“…A great deal of research has been directed at attempts to uncover the precise specificity of antilymphocyte antibodies in patients with SLE (12)(13)(14)(15)(16)(17)(18). If T cell reactivity can be demonstrated in some monoclonal anti-DNA antibodies, as shown in this report, and if this specificity actually represents a reaction between anti-DNA and DNA epitopes on living cell membranes, then it would appear that some of the autoantibody variation in SLE could be based on the same phenomenon.…”

Section: Discussionmentioning

confidence: 87%

Monoclonal murine anti‐dna antibody interacts with living mononuclear cells

Okudaira

Yoshizawa

Williams

1987

Arthritis & Rheumatism

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A monoclonal mouse antibody, 4-B-5, that reacted with both single-stranded DNA (ssDNA) and double-stranded DNA showed direct reactivity and cell association with mouse thymocytes, as well as peripheral blood mononuclear cells. Absorption of 4-B-5 with peripheral blood mononuclear cells or with mouse thymocytes markedly reduced reactivity with both ssDNA and double-stranded DNA. However, treatment of mouse thymocytes or human T cells with DNase completely eliminated monoclonal anti-DNA reactivity with cells. The cellular reactivity was completely restored when monoclonal anti-DNA was incubated with DNase-treated cells in the presence of normal human serum. Normal human serum was found to contain 574 f 639 ng/ml of ssDNA. Coincubation or cell preincubation of mouse thymocytes with ssDNA produced a marked increase in 4-B-5 cell association. These findings indicate that mouse monoclonal anti-DNA can react with and can penetrate both mouse and human mononuclear cells, and that this reactivity may depend on the presence of cell membrane DNA on both types of target cells.Previous studies from our laboratory have indicated that some sera from patients with systemic lupus Address reprint requests to Ralph C. Williams, Jr., MD, University of New Mexico School of Medicine, Albuquerque, NM 87131.Submitted for publication May 15, 1986; accepted in revised form October 2. 1986. erythematosus (SLE) contain IgG antilymphocyte antibodies which associate with T cells during in vitro culture and appear to penetrate cell membranes, as well as the inner cytosol of such living cells (1). The exact mechanism of how such IgG antibody reacts with T cell membranes and appears to enter cells without initially killing them is still not clear. It seemed possible that antinuclear antibodies might somehow react directly or cross-react with epitopes present on T cell membranes, and that this sort of cross-specificity might be involved in the eventual IgG cell membrane association.Recent observations support the idea that monoclonal anti-DNA antibodies may show a considerable degree of polyspecificity. Lafer et al(2) showed that such monoclonal lupus antibodies produced reactions with both polynucleotides and phospholipids. Jacob and coworkers (3) have subsequently demonstrated that monoclonal murine anti-DNA antibody binds to cell surface proteins which are not destroyed by DNase treatment. Moreover, these investigators have recently shown that monoclonal murine anti-DNA autoantibody binds to identical proteins present on human glomeruli, platelets, erythrocytes, T and B cells, and even neuronal tissue (4). This striking crossreactivity might somehow be associated with IgG anti-DNA T cell association in patients with SLE. This report describes our results measuring living mouse thymocyte or human peripheral blood mononuclear cell (PBMC) association with a panel of murine monoclonal IgG anti-DNA antibodies of varying specificity.

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Section: Discussionmentioning

confidence: 87%

Monoclonal murine anti‐dna antibody interacts with living mononuclear cells

Okudaira

Yoshizawa

Williams

1987

Arthritis & Rheumatism

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“…Yet, warm-reactive IgG ALA have also been reported in SLE (4). Although ALA are most likely heterogeneous in terms of antigenic reactivity, IgM ALA appear to preferentially recognize different isoforms of CD45, a transmembrane protein tyrosine phosphatase expressed in the surface of both B and T cells that plays a central role in lymphocyte homeostasis (5,6).…”

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Lupus IgG VH4.34 Antibodies Bind to a 220-kDa Glycoform of CD45/B220 on the Surface of Human B Lymphocytes

Cappione

Pugh‐Bernard

Anolik

et al. 2004

The Journal of Immunology

103

136

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Anti-lymphocyte autoantibodies are a well-recognized component of the autoimmune repertoire in human systemic lupus erythematosus (SLE) and have been postulated to have pathogenic consequences. Early studies indicated that IgM anti-lymphocyte autoantibodies mainly recognized T cells and identified CD45, a protein tyrosine phosphatase of central significance in the modulation of lymphocyte function, as the main antigenic target on T cells. However, more recent work indicates that lupus autoantibodies can also recognize B cells and that CD45 may also represent their antigenic target. In particular, IgM Abs encoded by VH4.34 appear to have special tropism for B cells, and strong, but indirect evidence suggests that they may recognize a B cell-specific CD45 isoform. Because VH4.34 Abs are greatly expanded in SLE, in the present study we investigated the antigenic reactivity of lupus sera VH4.34 IgG Abs and addressed their contribution to the anti-lymphocyte autoantibody repertoire in this disease. Our biochemical studies conclusively demonstrate that lupus IgG VH4.34 Abs target a developmentally regulated B220-specific glycoform of CD45, and more specifically, an N-linked N-acetyllactosamine determinant preferentially expressed on naive B cells that is sterically masked by sialic acid on B220-positive memory B cells. Strikingly, our data also indicate that this reactivity in SLE sera is restricted to VH4.34 Abs and can be eliminated by depleting these Abs. Overall, our data indicate that VH4.34 Abs represent a major component of the lupus IgG autoantibody repertoire and suggest that the carbohydrate moiety they recognize may act as a selecting Ag in SLE.

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“…Activated T cells, which exhibit a higher density of many surface membrane antigens than do resting cells and also express neoantigens, were found to be special targets of such autoantibodies [8]. Considerable information also has accrued concerning IgM ALAB target antigens: IL-2 receptor [9]; b 2 -microglobulin [10,11]; HLA class I heavy chains [12]; a DR framework epitope [13]; IgD, which functions as an antigen receptor on B cells [14]; B and T cell membrane glycosphingolipids [15]; CD45 [16][17][18]; and synthetic T cell receptor (TCR) peptides [19]. Almost certainly, there are additional specificities that have not yet been characterized.…”

mentioning

confidence: 99%

Are anti-ribosomal P protein antibodies a type of anti-lymphocyte antibody?

Winfield

1997

Clinical and Experimental Immunology

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Stafford and colleagues report in this issue that IgG anti-ribosomal P protein antibodies (anti-P) in systemic lupus erythematosus (SLE) bind to a human lymphocyte surface membrane-associated 38-kD molecule apparently identical to the P 0 ribosomal protein [1]. Their data extend those of Koren et al. [2], who demonstrated cell surface reactivity of anti-P with human hepatoma, neuroblastoma, and skin fibroblast cell lines. Although these are not novel observations-sporadic descriptions of cell surface binding by autoantibodies to various nuclear and intracytoplasmic antigens have been in the literature for 20 years (reviewed in [3])-special care was taken by Stafford to minimize the ambiguity inherent in experiments of this type. IgG Fc/Fc receptor interactions were ruled out. Specificity of binding was established by antigen inhibition, use of affinity-purified anti-P, and immunoblotting. Reactivity of anti-P with viable cells and ribosome-free plasma membrane preparations was demonstrated. And experiments with cell surface proteins purified by biotinylation revealed reactivity only with a 38-kD molecule, not the small P 1 and P 2 ribosomal proteins that would be expected if ribosomes released from dead cells were becoming attached to living cells. While it would have been nice to also have immunoprecipitation and complementdependent cytotoxicity data, and begging the question of how a ribosomal protein gets to the outer surface of the cell in the first place, Stafford's observations clearly support her conclusions that 'anti-ribosomal antibodies are a subset of anti-lymphocyte autoantibodies'.If anti-P antibodies are a subset of anti-lymphocyte antibodies (ALAB), they certainly differ from the traditional version, which are described below and in Table 1.Originally described as 'cold-lymphocytotoxins' because they kill lymphocytes in the presence of complement better at 15ЊC than at 37ЊC [4], classic IgM ALAB in SLE react broadly with autologous lymphocytes and with lymphocytes from unrelated donors (reviewed in [5]). Early studies established a relative specificity for T cells, especially thymocytes, and detected interesting specificities for functionally significant T cell subsets. IgM antibodies to B cells were described, as well, and are at least partially distinct from autoantibodies to T cells [6]. More recent data have substantially clarified the nature and potential significance of autoantibodies in this system. Thus, reactivity of T cells to IgM ALAB was shown to be dependent primarily on the presence of antigen(s) that are shared by CD4 + and CD8 + subsets, with a superimposed specificity for an additional antigen(s) expressed on CD4 + T cells [7]. Activated T cells, which exhibit a higher density of many surface membrane antigens than do resting cells and also express neoantigens, were found to be special targets of such autoantibodies [8] Most patients with SLE express IgM ALAB, which vary in titre with disease activity status in the same fashion as anti-dsDNA autoantibodies [6,20]. This association...

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Surface antigen specificity of cold‐reactive IgM antilymphocyte antibodies in systemic lupus erythematosus

Cited by 24 publications

References 28 publications

Monoclonal murine anti‐dna antibody interacts with living mononuclear cells

Monoclonal murine anti‐dna antibody interacts with living mononuclear cells

Lupus IgG VH4.34 Antibodies Bind to a 220-kDa Glycoform of CD45/B220 on the Surface of Human B Lymphocytes

Are anti-ribosomal P protein antibodies a type of anti-lymphocyte antibody?

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