Autoreactive B‐lymphocytes in SLE and RA patients: Isolation and characterisation using extractable nuclear and citrullinated antigens bound to immunobeads

Systemic lupus erythematosus and rheumatoid arthritis are autoimmune diseases characterised by B‐cell hyperactivation and production of autoantibodies (AutoAbs) against various self‐antigens, including extractable nuclear antigens and citrullinated peptides. Therefore, B lymphocytes and antibody‐secreting cells are considered relevant targets for therapies. However, isolation and characterisation of auto‐reactive specific B lymphocytes are limited, primarily due to technical issues. In this work, we purified extractable nuclear antigen‐specific and citrullinated peptide‐specific auto‐reactive B lymphocytes by magnetic selection with ENA‐ and citrullinated peptide‐bound immunobeads. We obtained blood auto‐reactive B lymphocytes from most patients. Their nature was primarily naïve B cells, some of them in an active status, with low levels of somatic hypermutations in the immunoglobulin heavy‐chain variable regions. Their presence correlated with serum levels of autoAb. Auto‐reactive B lymphocytes were able to differentiate into auto‐reactive antibody‐secreting cells under conditions of stimulation. In addition, based on the presence of circulating auto‐reactive B cells and/or antibody‐secreting cells, four different profiles were described in lupus patients. Thus, tracking auto‐reactive B cells and/or antibody‐secreting cells in patient blood could represent a biomarker for deciding whether to use therapies blocking either B cells, plasma cells or both, as well as a new tool for monitoring minimal residual autoimmune disease in patients.