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CUTTING EDGE |
* Institut National de la Santé et de la Recherche Médicale, Unité 454, Montpellier, France;
Département de Pharmacologie, Université de Montréal, Canada;
Laboratoire d’Immunologie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Limoges, France;
Laboratoire Cytokines, Université de Poitiers, France; and
¶ Zymogenetics, Seattle, WA 98102
IL-21 is a cytokine that regulates the activation of T and NK cells and promotes the proliferation of B cells activated via CD40. In this study, we show that rIL-21 strongly induces the production of all IgG isotypes by purified CD19+ human spleen or peripheral blood B cells stimulated with anti-CD40 mAb. Moreover, it was found to specifically induce the production of IgG1 and IgG3 by CD40-activated CD19+CD27– naive human B cells. Although stimulation of CD19+ B cells via CD40 alone induced 
1 and 3 germline transcripts, as well as the expression of activation-induced cytidine deaminase, only stimulation with both anti-CD40 mAb and rIL-21 resulted in the production of S/Sµ switch circular DNA. These results show that IL-21, in addition to promoting growth and differentiation of committed B cells, is a specific switch factor for the production of IgG1 and IgG3.
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