ANALYSIS OF THE V-KAPPA-III VARIABLE REGIONS OF POLYCLONAL RHEUMATOIDFACTORS ARISING DURING EPSTEIN-BARR-VIRUS INDUCED INFECTIOUS-MONONUCLEOSIS

The mechanisms that govern autoantibody production are still under deb ate. In particular, autoantibodies can appear as a consequence of a po lyclonal activation of B cells or as a consequence of an antigen drive n B cell expansion. The molecular analysis of the variable regions of auto-antibodies arising during different clinical situations can help to understand the origin of auto-antibodies. We recently described the main light chain variable regions of polyclonal rheumatoid factors oc curing during rheumatoid arthritis and suggested that the mutation pat tern of these regions could reflect an antigen driven process. Using t he same approach, we now report the molecular analysis of the same lig ht chain variable region containing a VKIII segment of rheumatoid fact ors originating from a polyclonal activation of B cells during an in v ivo Epstein-Barr virus infection, infectious mononucleosis. The cDNA d erived from rheumatoid factor synthetizing cells were amplified by two sets of polymerase chain reaction. The amplified products were cloned in M13mp19 phages and sequenced. The nucleotide analysis of the VKIII containing VK regions shows that: 1) the rheumatoid factor activity i s associated with the 3 VKIII genes (Kv 325, Kv 328 and Vg) already kn own to encode for monoclonal and polyclonal rheumatoid factors, 2) the re is a preferential use of Kv 328 and Vg, each one of these genes bei ng poorly mutated, 3) the CDR mutation rates of these genes is no high er than the framework mutation rates, 4) there is a restriction of the JK usage: Kv 328 derived gene segments rearrange exclusively with JK1 , Vg preferentially rearranges with JK1 and JK4. These results mainly suggest that naturally occuring polyclonal activation of autoreactive B cells produces poorly mutated autoantibodies.