Monoclonal B Cell Expansion and Antigen-driven Somatic Hypermutation of Ig VH Genes in Synovial Membrane of Patients with Crystal-Induced Arthritis (129.3)

Abstract

Abstract The mechanisms underlie the inflammation in crystal-induced arthropathies (CyA) is not fully understood. Inflammatory mediators, like crystal-specific antibodies and macrophages have been explored as possible factors in the generation or progression of CyA. To examine whether B cells are involved in the pathogenesis of CyA, we analyzed immunoglobulin (Ig) heavy chain variable region (VH) genes of B cells from synovial membrane of five CyA patients. Using a RT-PCR technique, we could detect rearrangements of Ig VH genes in all five cases. Sequence analysis of CDR3 region of rearranged VDJ genes revealed a monoclonal B cell expansion in four out of five CyA patients. The nucleotide sequences of VH genes from clonally expanded B cells demonstrated the heterogeneous usage of the Ig VH gene family. All expanded B cell clones showed somatic mutations in the CDRs with a high replacement-to-silent ratio (> 2.9) and were distributed in a way suggesting that these B cells had been positively selected through their antigen receptor. The intraclonal variations is also common, indicate that consistent antigen stimulation is close related to CyA development. These data demonstrate that there are antigen-driven clonal accumulations of B cells in CyA synovial membrane. Whether these antibodies are specific to crystal epitopes is currently under investigation. This study was supported by the NIH Grant RO1 AI 54911.