Amara, Khaled Steen, Johanna Murray, Fiona Morbach, Henner Fernandez-Rodriguez, Blanca M. Joshua, Vijay Engström, Marianne Snir, Omri Israelsson, Lena Catrina, Anca I. Wardemann, Hedda Corti, Davide Meffre, Eric Klareskog, Lars Malmström, Vivianne 2013-02-25 Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, many features of these antibodies, including their site of production and the extent of MHC class II–driven T cell help, remain unclarified. To address these questions, we have used a single B cell–based cloning technology to isolate and express immunoglobulin (Ig) genes from joint-derived B cells of active RA patients. We found ∼25% of synovial IgG-expressing B cells to be specific for citrullinated autoantigens in the investigated ACPA+ RA patients, whereas such antibodies were not found in ACPA− patients. The citrulline-reactive monoclonal antibodies did not react with the unmodified arginine peptides, yet several reacted with more than one citrullinated antigen. A role for active antigen selection of the citrulline-reactive synovial B cells was supported by the strong bias toward amino acid replacement mutations in ACPA+ antibodies and by their loss of reactivity to citrullinated autoantigens when somatic mutations were reverted to the corresponding germline sequences. application/pdf https://n2t.net/ark:/12658/srd1318861 https://susi.usi.ch/global/documents/318861 https://susi.usi.ch/documents/318861/files/Amara_JEM_2013.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20121486 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318861 info:eu-repo/semantics/openAccess CC BY-NC-SA The journal of experimental medicine. - 2013, vol. 210, no. 3, p. 445-455 info:eu-repo/classification/udc/61 Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition http://purl.org/coar/resource_type/c_6501