Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and autoantibody production. As spleen tyrosine kinase (Syk) is pivotal in B cell activation, these experiments aimed to examine the extent to which Syk was abnormally expressed in SLE B cells and the nature of the B cell subset that differently expressed Syk. Methods. B cells from healthy donors and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated Syk. B cell subsets expressing higher levels of Syk were found, and their detailed phenotype, in vitro differentiation into plasmablasts/ plasma cells, and Syk induction by cytokines were determined. Results. Syk expression was higher in CD27 memory B cells than in naive B cells from SLE patients. However, a significantly increased frequency of CD27 B cells with bright expression of Syk (Syk ) was found in SLE patients. CD27 Syk B cells showed enhanced basal expression of p-Syk and stronger Syk phosphorylation upon B cell receptor (BCR) engagement as compared to CD27 Syk B cells. CD27 Syk B cells were CD38 as well as CD19 , CD20 , and mainly CD21 , with decreased ABCB1 transporter activity. In contrast to CD27 Syk B cells, CD27 Syk B cells exhibited enhanced differentiation into CD27 IgG-secreting cells and expressed somatically mutated BCR gene rearrangements. Syk B cells were inducible in vitro by stimulation with interferon-, lipopolysaccharide, or tumor necrosis factor . Conclusion. SLE patients exhibit an increased frequency of hitherto unknown CD27 Syk memorylike B cells, indicating that intracellular Syk density could distinguish CD27 memory B cells from truly naive B cell subsets. Furthermore, the CD27 Syk subset is a candidate for a source of increased plasma cells in SLE.