Objective The origins of the self-reactive B cells in the autoimmune diseases systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are unknown, but clusters of B, T and dendritic cells, which may act as foci for presentation of self-antigens, are seen in rheumatoid synovial membranes and vasculitic lesions of SLE patients. The objectives of this project are to identify the germline Ig V-genes expressed by the B cells in these clusters, to analyse the pattern of somatic hypermutation in the expressed V-genes and from this, the family history of development of self-reactive B cell clones and whether they are driven by antigen selection. Clusters of lymphocytes will be excised from stained sections of rheumatoid synovia and vasculitic lesions by micromanipulation. Recombined Ig V-genes will be amplified by PCR, cloned, sequenced and the number of B cell clones which have arisen from independent Ig V-gene recombinations determined. Family trees will be constructed showing the relationships between clone members by the pattern of V-region somatic hypermutation. In a normal immune response, competition for antigen results in selection of B cells with a high replacement to silent (R/S) ratio in hypervariable regions. The R/S ratios of the B cell clones from SLE and RA patients will be analysed to determine whether antigen selection is driving B cell proliferation in the cell clusters. Amino acid substitutions which occur repeatedly, indicative of affinity maturation, will be identified. Fields of science medical and health sciencesclinical medicinerheumatologyhumanitieshistory and archaeologyhistorymedical and health sciencesbasic medicineimmunologyautoimmune diseasesnatural scienceschemical sciencesorganic chemistryamines Programme(s) FP4-TMR - Specific research and technological development programme in the field of the training and mobility of researchers, 1994-1998 Topic(s) 0302 - Post-doctoral research training grants TL07 - Immunology and Cancer Call for proposal Data not available Funding Scheme RGI - Research grants (individual fellowships) Coordinator Deutsches Rheumaforschungszentrum Berlin EU contribution No data Address 2,Monbijoustrasse 10117 Berlin Germany See on map Total cost No data Participants (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all Not available United Kingdom EU contribution No data Address See on map Total cost No data
