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 (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine rheumatology
- humanities history and archaeology history
- medical and health sciences basic medicine immunology autoimmune diseases
- natural sciences chemical sciences organic chemistry amines
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
10117 Berlin
Germany
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