{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:02:41Z","timestamp":1781305361236,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T00:00:00Z","timestamp":1416873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB650, 633"],"award-info":[{"award-number":["SFB650, 633"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<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\u2212 B cells with bright expression of Syk (Syk++) was found in SLE patients. CD27\u2212Syk++ B cells showed enhanced basal expression of p\u2010Syk and stronger Syk phosphorylation upon B cell receptor (BCR) engagement as compared to CD27\u2212Syk+ B cells. CD27\u2212Syk++ B cells were CD38\u2212 as well as CD19++, CD20++, and mainly CD21\u2212, with decreased ABCB1 transporter activity. In contrast to CD27\u2212Syk+ B cells, CD27\u2212Syk++ B cells exhibited enhanced differentiation into CD27++ IgG\u2010secreting cells and expressed somatically mutated BCR gene rearrangements. Syk++ B cells were inducible in vitro by stimulation with interferon\u2010\u03b3, lipopolysaccharide, or tumor necrosis factor \u03b1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SLE patients exhibit an increased frequency of hitherto unknown CD27\u2212Syk++ memory\u2010like B cells, indicating that intracellular Syk density could distinguish CD27\u2212 memory B cells from truly naive B cell subsets. Furthermore, the CD27\u2212Syk++ subset is a candidate for a source of increased plasma cells in SLE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38854","type":"journal-article","created":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T11:59:48Z","timestamp":1408708788000},"page":"3424-3435","source":"Crossref","is-referenced-by-count":50,"title":["Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"66","author":[{"given":"Sarah J.","family":"Fleischer","sequence":"first","affiliation":[{"name":"Charit\u00e9 University Medicine Berlin and German Rheumatism Research Center Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Giesecke","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medicine Berlin and German Rheumatism Research Center Berlin Berlin 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