{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:35:59Z","timestamp":1791326159949,"version":"4.3.1"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although recent studies indicated that IL-21 is an important regulator of human B cell activation, detailed comparison of the effects of IL-21 on distinct B cell subsets have not been performed. Our studies revealed that IL-21R is expressed by naive and germinal center B cells, but not memory or plasma cells. IL-21R was increased on naive and memory B cells following in vitro activation. Investigation into the kinetics and magnitude of responses of human B cells to IL-21 revealed that IL-21 potently augmented proliferation of CD40L-stimulated neonatal, splenic naive, and memory and tonsil germinal center B cells. This response exceeded that induced by IL-4, IL-10, and IL-13, cytokines that also induce B cell proliferation. Remarkably, CD40L\/IL-21-stimulated naive B cells underwent the same number of divisions as memory cells and exhibited a greater enhancement in their response compared with CD40L alone than memory B cells. Therefore, IL-21 is a powerful growth factor for naive B cells. This may result from the higher expression of IL-21R on naive, compared with memory, B cells. Stimulation of human B cells with CD40L\/IL-21 also induced IL-10 production and activation of STAT3. We propose that IL-21 may have therapeutic application in conditions of immunodeficiency where it could expand naive B cells, the predominant B cell subset in such patients. Conversely, because IL-21 is increased in murine models of lupus, dysregulated IL-21 production may contribute to perturbed B cell homeostasis observed in systemic lupus erythematosus. Thus, antagonizing IL-21 may be a novel strategy for treating Ab-mediated autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.177.8.5236","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:20:27Z","timestamp":1397848827000},"page":"5236-5247","source":"Crossref","is-referenced-by-count":251,"title":["Kinetics of Human B Cell Behavior and Amplification of Proliferative Responses following Stimulation with IL-21"],"prefix":"10.1093","volume":"177","author":[{"given":"Kim L","family":"Good","sequence":"first","affiliation":[{"name":"Centenary Institute of Cancer Medicine and Cell Biology , New South Wales ,","place":["Australia"]},{"name":"Faculty of Medicine, University of Sydney , New South Wales ,","place":["Australia"]},{"name":"Garvan Institute of Medical Research , New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa L","family":"Bryant","sequence":"additional","affiliation":[{"name":"Centenary Institute of Cancer Medicine and Cell Biology , New South Wales ,","place":["Australia"]},{"name":"Faculty of Medicine, University of Sydney , New South Wales ,","place":["Australia"]},{"name":"Garvan Institute of Medical Research , New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart G","family":"Tangye","sequence":"additional","affiliation":[{"name":"Centenary Institute of Cancer Medicine and Cell Biology , New South Wales ,","place":["Australia"]},{"name":"Garvan Institute of Medical Research , New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,10,15]]},"reference":[{"key":"2026020211115542000_R1","first-page":"54","volume-title":"Science","year":"1996"},{"key":"2026020211115542000_R2","first-page":"172","volume-title":"Curr. 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