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. CONCLUSION: 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.
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Authors | Sarah J Fleischer, Claudia Giesecke, Henrik E Mei, Peter E Lipsky, Capucine Daridon, Thomas Dörner |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 66
Issue 12
Pg. 3424-35
(Dec 2014)
ISSN: 2326-5205 [Electronic] United States |
PMID | 25156507
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 by the American College of Rheumatology. |
Chemical References |
- Intracellular Signaling Peptides and Proteins
- Tumor Necrosis Factor Receptor Superfamily, Member 7
- Protein-Tyrosine Kinases
- SYK protein, human
- Syk Kinase
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Topics |
- Adult
- Aged
- B-Lymphocyte Subsets
(enzymology, immunology)
- Case-Control Studies
- Cell Differentiation
(immunology)
- Female
- Flow Cytometry
- Humans
- Immunologic Memory
(immunology)
- Intracellular Signaling Peptides and Proteins
(metabolism)
- Lupus Erythematosus, Systemic
(enzymology, immunology)
- Male
- Middle Aged
- Phosphorylation
- Plasma Cells
(enzymology, immunology)
- Protein-Tyrosine Kinases
(metabolism)
- Syk Kinase
- Tumor Necrosis Factor Receptor Superfamily, Member 7
(metabolism)
- Young Adult
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