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^a Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
^b Department of Medicine, University College, London W1P 9PG, United Kingdom
^c Department of Histopathology, Imperial College School of Medicine, London W12 0NN, United Kingdom
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.44-1223-41217844-1223-4022455

msn{at}mrc-lmb.cam.ac.uk

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.

Key Words: immunodeficiency • autoimmunity • B lymphocyte • secretory IgM

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