Editorial POLYCLONAL B CELL ACTIVATION AND MECHANISMS OF AUTOANTIBODY PRODUCTION IN SLE ANTIGEN-DRIVEN ANTIBODY RESPONSE AS

The pathogenic role of lupus anticoagulant or anticardiolipin antibodies (members of the broader class of antiphospholipid antibodies) in systemic lupus erythematosus (SLE) is suggested by their strong clinical association with thrombocytopenia, thrombosis, and multiple spontaneous abortions. In this issue of Autoimmunity, Q. Meng and J. Rauch show that some SLE anticoagulant antibodies are substantially different in their antigen-binding activity from anticoagulant antibodies detectable in healthy subjects. The authors found that a major proportion of the monoclonal autoantibodies they generated by fusion of B lymphocytes from SLE patients were functionally monoreactive, that is, they bound only one of the self-antigens tested. These antigens included platelets, phospholipids of different composition, dsDNA, and various components of the coagulation cascade. In contrast, the “autoantibodies” they generated, using a similar methodology from healthy subjects, were polyreactive, that is, they bound to most or all self-antigens tested. Moreover, most of monoclonal platelet-binding autoantibodies derived from SLE patients, but none of those from healthy subjects, displayed an efficient cytotoxic activity. These findings suggest that a major component of the anticoagulant and, more in general, of the anti-self antibody response in SLE displays the exquisite antigen-binding specificity characteristic of an actively antigen-induced antibody response. Antibodies binding self-antigens have been considered by definition a characteristic feature of autoimmune patients. A large body of experimental data, however, have shown in the last years that similar antibodies can be produced by lymphocytes in the normal B cell repertoire’.’. These “autoantibodies”, mostly IgM, but also IgG and IgA, are p~lyreactive~.~ and constitute the class of Ig known as “natural antibodies” or “natural autoantibodies”’.’. Their antigen-binding sites are encoded in variable gene segments in germ-line configuration’. Natural antibodies are produced by a discrete lymphocyte subset, CDS+B cells, a major component of the human B cell repertoires-’. Their role is likely that of first line of defense against invading microorganisms’,’. Because of their ability to bind self-antigens, it has been tempting to speculate that polyreactive antibodies may play some role in autoimmunity. However,