Diminished B cell response and peripheral B cell abnormalities in patients with SLE are linked to disturbances of the spleen tyrosine kinase (P4056)

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, autoantibody production, B cell hyperreactivity and an impaired B cell homeostasis. Recent data suggested that an impaired B cell response could also lead to autoimmunity. In this study, the BCR downstream signaling spleen tyrosine kinase Syk of healthy donors (HD), SLE, rheumatoid arthritis (RA) and primary Sjögren’s syndrome (pSS) patients was analyzed in detail and revealed new insights into peripheral B cell abnormalities based on intracellular characteristics. Interestingly, SLE B cells showed a significantly lower but long-lasting Syk (Y352) phosphorylation after BCR engagement compared to HD (p<0.05). Furthermore, a significant enlarged frequency of Syk(bright) B cell population has been identified within the CD27(-) B cell subset in the blood of SLE patients (p<0.001), but no correlation with the disease activity was observed. Notably, the frequency of Syk(bright) B cells was not increased in RA or pSS patients. Further characterization showed that Syk(bright) cells exhibit an increased basal level of phosphorylated Syk, expressed higher levels of CD19 and CD95 and mainly do not express CD38 as compared to Syk(dim) cells. Thus, SLE patients show a diminished but long-lasting BCR response and exhibit an enlarged unique Syk(bright) B cell subset that could be responsible for the hyperactivity of SLE B cells.