A SOLUTION TO THE RHEUMATOID-FACTOR PARADOX - PATHOLOGICAL RHEUMATOIDFACTORS CAN BE TOLERIZED BY COMPETITION WITH NATURAL RHEUMATOID FACTORS

Rheumatoid factors (RF) associated with arthritic joint erosion are on ly seen transiently, if at all, in nondiseased individuals, Therefore, a tolerance mechanism must exist that prevents pathologic RF B cells from expressing Abs, Surprisingly, it has been shown that pathologic R F B cells are not tolerized by any previously established tolerance me chanism such as deletion, receptor editing, anergy, or prevention of m emory establishment, How are pathologic RF cells tolerized? By simulat ing the RF response with a cellular automaton model immune system, we demonstrate that pathologic RFs can be tolerized by the novel mechanis m of ''competitive tolerance'' with natural, nonpathologic RFs, We the n demonstrate that competitive tolerance can be broken when a sequeste red pool of expanding B cells are inappropriately subjected to chronic stimulation (as appears to occur in MRL/lpr mice and in patients with rheumatoid arthritis).