title: Increased frequency of a unique spleen tyrosine kinase bright memory B cell population in systemic lupus erythematosus.
abstract: 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-γ, lipopolysaccharide, or tumor necrosis factor α.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Charité University Medicine Berlin and German Rheumatism Research Center Berlin, Berlin, Germany.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Fleischer
authors.forename: Claudia
authors.initials: C
authors.lastname: Giesecke
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Mei
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Capucine
authors.initials: C
authors.lastname: Daridon
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010950:Plasma Cells / Q000201:enzymology* / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000072377:Syk Kinase; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase