COMPARISON OF RHEUMATOID FACTORS OF RHEUMATOID-ARTHRITIS PATIENTS, OFINDIVIDUALS WITH MYCOBACTERIAL INFECTIONS AND OF NORMAL CONTROLS - EVIDENCE FOR MATURATION IN THE ABSENCE OF AN AUTOIMMUNE-RESPONSE

We analyzed the rheumatoid factors (RF) produced by Epstein-Barr virus -transformed monoclonal B cells established from four patients with rh eumatoid arthritis (RA), three individuals with a history of Mycobacte rium tuberculosis (TB) and four normal controls (NI), Fifty-eight RF w ere analyzed for specific activity (international units-RF/mu g) for t he Fe part of IgG and their interaction with tetanus toxoid (TT) and D NA (polyspecificity). Furthermore, we sequenced the V-D-J heavy chain region of IG (9TB-/7RA-) RE Significant differences were observed betw een tile NT-RF and the TB- and RA-RE While the RF repertoire of normal individuals comprised of low-avidity RF of which the majority (15/17) were polyspecific, more than half of the TB- and RA-RF were monoreact ive. Furthermore, the monospecific TB- and RA-RF were of signifi cantl y higher avidity than the NI-RF (RA > TB much greater than NI), With r espect to polyspecificity, the RF in the three groups were comparable: the interaction with DNA, TT as well as with Fc was inhibited either by an increase of the ionic strength to 0.3-0.5 M NaCl or by addition of the polyanion dextran sulfate, indicating that the antibodies inter acted with similar anionic epitopes shared by the three antigens. Anal ysis of the V-D-J heavy chain regions showed significant diferenccs be tween the respective RF. The salt-sensitive binding was highly correla ted with the presence of arginine in the complementarity-determining r egion 3 (CDR3). Furthermore, whereas the polyspecific RF consisted pre dominantly of germ-line encoded antibodies, the genes of the monospeci fic RA/TB-RF were somatically mutated (RA > TB). It is therefore likel y that maturation of RF can be initiated by chronic infections and tha t monospecific, somatically mutated RF are not a unique characteristic of autoimmune diseases.