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Review
. 2016 Dec:43:1-7.
doi: 10.1016/j.coi.2016.07.002. Epub 2016 Aug 6.

DNA-reactive B cells in lupus

Jolien Suurmond  1 , Justine Calise  2 , Susan Malkiel  1 , Betty Diamond  3
Affiliations
Review

DNA-reactive B cells in lupus

Jolien Suurmond et al. Curr Opin Immunol. 2016 Dec.

Abstract

IgG anti-DNA antibodies are both diagnostic and pathogenic for systemic lupus erythematosus (SLE). They contribute to tissue inflammation through direct tissue binding and to systemic inflammation through activation of Toll-like receptors by nucleic acid-containing immune complexes. IgG DNA-reactive antibodies originate when B cell tolerance mechanisms are impaired. The heterogeneous immune perturbations in SLE lead to the survival and activation of DNA-reactive B cells in various B cell subsets at distinct stages of B cell maturation and differentiation. We propose that the spectrum of B cell alterations and failed tolerance mechanisms for DNA-reactive B cells in lupus patients is best understood by studying genetic risk alleles. This implies that the B cells producing IgG anti-DNA antibodies and the failed tolerance mechanisms(s) will differ across patients. A better understanding of these differences should lead to better patient stratification, improved outcomes of clinical trials, and the identification of novel therapeutic targets.

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Figures

Figure 1
Figure 1
Inflammatory feed-forward loop for anti-DNA responses.
Figure 2
Figure 2
Tolerance checkpoints for DNA-reactive B cells in humans. The percentages of DNA-reactive B cells in each subset are derived from references 17–20, 23, 25. Markers to identify the different populations in these studies are indicated in the top of the figure. N.d. not determined.
See this image and copyright information in PMC

References

    1. Gaynor B, Putterman C, Valadon P, Spatz L, Scharff MD, Diamond B. Peptide inhibition of glomerular deposition of an anti-DNA antibody. Proc Natl Acad Sci U S A. 1997;94:1955–1960. - PMC - PubMed
    1. Raz E, Brezis M, Rosenmann E, Eilat D. Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney. J Immunol. 1989;142:3076–3082. - PubMed
    1. Clynes R, Dumitru C, Ravetch JV. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science. 1998;279:1052–1054. - PubMed
    1. Lovgren T, Eloranta ML, Bave U, Alm GV, Ronnblom L. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 2004;50:1861–1872. - PubMed
    1. Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest. 2005;115:407–417. - PMC - PubMed

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