IgVH genes from different anatomical regions, with different histopathological patterns, of a rheumatoid arthritis patient suggest cyclic re-entry ofmature synovial B-cells in the hypermutation process

In the present study 55 IgVH genes amplified from three different anatomica l regions of a rheumatoid arthritis (RA) patient were analyzed, adding furt her information on synovial B-cell maturation and recirculation in RA. This analysis demonstrated somatically mutated IgVh genes in all regions studie d, with amino acid deletions and mixed IgVh molecules, suggesting the exist ence of a novel pathway to generate (auto) antibody specificities. Comparis on of amino acid sequences of amplified genes that belong to the VH1 family (with predominantly the same germline counterpart) exhibited strong homolo gy, indicating an apparently conserved mutational pattern. This suggests th at the number of antigens that activate B cells in different locations is r estricted. The most striking result was the finding of clonally related seq uences in different anatomical regions, indicating a recirculation of activ ated B cells between the different affected joints.