title: Deficiency in serum immunoglobulin (Ig)M predisposes to development of IgG autoantibodies.
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.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom.
authors.forename: M R
authors.initials: MR
authors.lastname: Ehrenstein
authors.forename: H T
authors.initials: HT
authors.lastname: Cook
authors.forename: M S
authors.initials: MS
authors.lastname: Neuberger
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002460:Cell Line; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007148:Immunoglobulin mu-Chains / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains