Rheumatoid Synovial B-Cells Show Hypermutated VH genes With Aminoacid's Deletions on the Complementarity Determining Regions

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 33 (F 31). 1998;

Abstract: Pathologisches Institut- 1Orthopädische Klinik Univ. Würzburg DRFZ Berlin Introduction: The existence of germinal center-like structures in the synovial tissue of rheumatoid arthritis (RA) patients makes a B-cell affinity maturation very likely. The aim of this study was to prove the existence of that affnity maturation by showing that related B-cell clones with different mutational stages are present in Ihe RA synovial tissue. Methods: RNA was prepared from tissue sections of 3 RA patients (for one patient sections from two different joints were used). The corresponding cDNA was amplified using a set of specific VH primers and the variable regions were sequenced on a sequencing machine (MWG Biotech). The obtained sequences were compared with the germline genes on the EMBL/Genbank data base. Results: All the obtained sequences were mutated eventhough only 67 % showed affinity maturation (R/S > 2 in the complementarity determining regions). The V genes of the VH1 and VH5 class had the higher expression. The VH1 DP-10 germline gene presented for the same patient two distinct mutational stages the VH1 DP-14 germline gene presented for the same patient two distinct mutational stages occuring in one of them 2 aminoacid's deletions on the complementarity determining regions. For the VH5 DP-73 germline gene four different mutational stages were present in one patient and two in another patient. Conclusions: The presence of B-cell clones presenting different mutational patterns from a specific germline gene on the synovial tissue of RA patients confirms the existence of a local affnity maturation. ... le

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