Increased frequency of a unique spleen tyrosine kinase bright memory B cell population in systemic lupus...

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.

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.

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-γ, lipopolysaccharide, or tumor necrosis factor α.

SLE patients exhibit an increased frequency of hitherto unknown CD27-Syk++ memory-like 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.