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Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus
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| Zeitschriftentitel: | Arthritis & Rheumatology |
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| Personen und Körperschaften: | , , , , , |
| In: | Arthritis & Rheumatology, 66, 2014, 12, S. 3424-3435 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| Zusammenfassung: | <jats:sec><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec> |
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| Umfang: | 3424-3435 |
| ISSN: |
2326-5191
2326-5205 |
| DOI: | 10.1002/art.38854 |