IgM autoimmunity and neoplasia

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Owing to their broad antiself antigen reactivity, natural IgM antibodies could provide the templates for affinity matured class-switched autoantibodies, and B-l cells can, under certain circumstances, play a role in the establishment of autoimmune phenomena. B-l cells are greatly increased in a number in patients with rheumatoid arthritis and Sjogren's syndrome. In rheumatoid arthritis patients, these cells spontaneously proliferate and secrete large amounts of IgM with RF activity. Some of these IgM RF are polyreactive, display a low affinity for the IgG Fc fragment, and are encoded by unmutated V genes. Others are monoreactive, display a higher affinity for

IgG Fc fragment (Kj, ICT.vr1), and are encoded by extensively mutated V genes. The inherent proliferative potential of IgM-producing B-l cells and their stimulation by antigen may be synergistic and may contribute to premalignant or malignant B lymphoid transformation. A relatively high incidence of B lymphoid malignancies occurs in patients with Sjogren's syndrome and rheumatoid arthritis. Further evidence pointing to a link between IgM-producing B-l cells, autoimmunity and malignant transformation stems from the features of the monoclonal antibodies associated with a variety of human B cell neoplasms, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, Waldenstrom's macroglobulinemia and other paraproteinemias. The vast majority of CLL B cells are B-1 and produce, in general, IgM. Like monoclonal Waldenstrom's IgM paraproteins, many of these monoclonal IgM possess RF and other antiself antigen reactivities. Other autoantibodies of the IgM class that are characteristically associated with malignant B cell neoplasia or benign monoclonal gammopathy are cold agglutinins that react with various polysaccharide red cell determinants. Transient cold agglutinins of the same IgM class and similar antigen-reactivity occur commonly in patients with infections, particularly those by Mycoplasma pneumoniae or by Epstein-Barr virus (infectious mononucleosis). Thus, the neoplastic transformation of natural IgM antibody-producing B clono-types is associated with fidelity of the function defining the physiological B cell clonotypic progenitor.

See also: Affinity; Antigen-binding site; B lymphocyte activation; Complement, classical pathway; Idiotype network; Immunoglobulin genes; Joining J chain; Leukemia; Natural antibodies; Rheumatoid arthritis, animal models; Rheumatoid arthritis, human; Sjögrens syndrome; Systemic lupus erythematosus, experimental models; Systemic lupus erythematosus (SLE), human.

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