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Contenido archivado el 2024-04-30

Analysis of the development of b cell clones and somatic hypermutation in autoimmune disease

Objetivo



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.

Ámbito científico (EuroSciVoc)

Programa(s)

Tema(s)

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

RGI - Research grants (individual fellowships)

Coordinador

Deutsches Rheumaforschungszentrum Berlin
Aportación de la UE
Sin datos
Dirección
2,Monbijoustrasse
10117 Berlin
Alemania
Coste total
Sin datos

Participantes (1)