English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

ADVANCES in molecular biological and human cell hybridization technology significantly enhanced our knowledge of human immunoglobulin variable region (IgV) gene organization, structure and expression. These advances have also provided insight into autoimmunity and mechanisms that may determine the nature of the antibody repertoire expressed in RA patients. Since the specificity for antigens is determined by the precise sequence of amino acids used in the antigenbinding site, studies in autoimmune diseases have focused on the combinatorial events and mutations which occur in genes that encode autoantibodies. Explicitly, the question has been whether autoantibodies are direct copies of germline genes, or products of somatic mutations. Non-random distribution of replacement mutations in rearranged IgV genes, compared with their germline counterparts, is indicative of antigen-driven selection of B-lymphocytes [1]. In contrast, the lack of mutations, or evidence of limited random mutations, is indicative of non-specific polyclonal activation. IgV genes have also been used as markers of clonal relatedness of autoantibodies because unique combinations of VH, DH and JH or VL and JL elements, formed during B-lymphocyte differentiation and maturation are retained by cells derived from the same progenitor pre-B cell [2]. The evidence from examining IgV gene sequences in RA patients shows that almost all IgM RF and 50% of IgG derived from B-lymphocyte hybridomas or EBVlines producing monoclonal immunoglobulins are encoded by genes in their germline configuration, or with very few nucleotide changes from known germline genes [3-5]. Interestingly, studies of B-lymophocyte ontogeny have revealed that the same genes are also widely transcribed in early foetal and neonatal B-lymphocytes [6,7]. Moreover, these studies suggested that during early life only a restricted set of genes from a large pool of available genes are used, and that the repertoire diversifies progressively after birth until a normalization of IgV gene use is achieved [8]. One explanation for restricted gene use during early life is that these genes are of special survival value and function before more specialized adaptive responses involving somatic diversification permits the generation of antibodies able to recognize the extensive range of environmental antigens. Recent studies of B-lymphocyte repertoire in normal individuals suggested that B-lymphocytes expressing these genes may also participate in interconnections between Tand B-lymphocytes to maintain homeostasis within the immune system [9]. The overexpression of these genes in RA

RHEUMATOID FACTORS AND GERMLINE GENES IN RHEUMATOID ARTHRITIS: EVIDENCE OF AN INTRINSIC B-LYMPHOCYTE DEFECT?