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. 2000 Apr 3;191(7):1253-8.
doi: 10.1084/jem.191.7.1253.

Deficiency in serum immunoglobulin (Ig)M predisposes to development of IgG autoantibodies

M R Ehrenstein  1 , H T Cook, M S Neuberger
Affiliations

Deficiency in serum immunoglobulin (Ig)M predisposes to development of IgG autoantibodies

M R Ehrenstein et al. J Exp Med. .

Abstract

Serum immunoglobulin (Ig)M provides the initial response to foreign antigen and plays a regulatory role in subsequent immune response development, accelerating the production of high-affinity IgG. Here we show that mice deficient in serum IgM have an increased propensity to spontaneous autoimmunity as judged by the development with age of serum IgG anti-DNA antibodies and the renal deposition of IgG and complement. They also exhibit augmented anti-DNA IgG production on exposure to lipopolysaccharide. Thus, deficiency in serum IgM leads to diminished responsiveness to foreign antigens but increased responsiveness to self-a paradoxical association reminiscent of that described in humans deficient in complement or IgA. We wondered whether serum IgM might play an analogous role with regard to the response to self-antigens. However, here-in contrast to the sluggish response to foreign antigens-we find that deficiency in serum IgM actually predisposes to the development of IgG antibodies to autoantigens.

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Figures

Figure 1
Figure 1
(A) Titers of IgG anti-dsDNA and total IgG in the sera of 12–18-mo-old litter-matched μs −/μs − and μs +/μs + mice. A line at 0.24 U/ml marks an IgG anti-dsDNA titer 3 SEM above the average titer of the μs +/μs + controls. The IgG anti-dsDNA titers in sera from 18–20-mo-old mice generated from control (129 × C57BL/6)F2 breedings (labeled F2) are shown for comparison. (B) Titers of IgG anti-dsDNA in the IgG fraction of sera of 12–18-mo-old litter-matched μs −/μs − and μs +/μs + mice. The IgG fractions were obtained by purification on protein G–Sepharose. (C) ELISA titration of autoantibodies in μs −/μs − mice. Open symbols are from μs −/μs − mice, filled symbols from representative μs +/μs + controls. The μs −/μs − sera illustrated harboring anti-dsDNA antibodies are from mice 9128 and 9383; the two sera with elevated anticardiolipin antibodies are from mice 9206 (which also harbors IgG anti-dsDNA; see Table ) and 9484; the mouse harboring antibodies to myeloperoxidase is 9296. (D) Binding kinetics of the anti-DNA antibodies as measured by surface plasmon resonance. Antibody binding to a biotinylated dsDNA oligodeoxyribonucleotide immobilized on a streptavidin chip is depicted in resonance units and was monitored as a function of time. After ∼4 min, residual IgG bound to the chip was identified using a polyclonal anti–mouse IgG antiserum. The dashed line depicts the same experiment performed using serum from a control mouse that did not exhibit IgG anti-dsDNA. (E) Immunofluorescence of Crithidia with serum (diluted 1:20) from μs −/μs − mouse 9383 reveals characteristic staining of the nucleus and kinetoplast.
Figure 2
Figure 2
IgG deposits in the kidneys of μs −/μs − mouse 9128 (and μs +/μs + mouse 9332 as control) detected by immunohistochemistry (original magnification: ×100; 1-s exposure).
Figure 3
Figure 3
Titers of IgG anti-dsDNA antibodies and total IgG in the sera of 3-mo-old μs −/μs − and μs +/μs + mice before (Pre) and after (Post) administration of LPS.
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References

    1. Boes M, Esau C., Fischer M.B., Schmidt T., Carroll M., Chen J. Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM. J. Immunol. 1998;160:4776–4787. - PubMed
    1. Ehrenstein M.R, O'Keefe T.L., Davies S.L., Neuberger M.S. Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response. Proc. Natl. Acad. Sci. USA. 1998;95:10089–10093. - PMC - PubMed
    1. Mohan C., Shi Y., Laman J.D., Datta S.K. Interaction between CD40 and its ligand gp39 in the development of lupus nephritis. J. Immunol. 1995;154:1470–1480. - PubMed
    1. O'Keefe T.L., Williams G.T., Batista F.D., Neuberger M.S. Deficiency in CD22, a B cell–specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies. J. Exp. Med. 1999;189:1307–1313. - PMC - PubMed
    1. Cavallo T., Granholm N.A. Lipopolysaccharide from gram-negative bacteria enhances polyclonal B cell activation and exacerbates nephritis in MRL/lpr mice. Clin. Exp. Immunol. 1990;82:515–521. - PMC - PubMed

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