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. 2014 Feb 18;5:65. doi: 10.3389/fimmu.2014.00065

Figure 2.

Figure 2

Cytokine-induced differentiation of human B cells in vitro: requirement for IL-21 signaling in vivo. In vitro studies demonstrated that human B cells could undergo events such as Ig class switching and differentiation to become Ig-secreting cells following stimulation with a diverse range of cytokines. However, analysis of individuals with hypomorphic mutations in genes encoding STAT3, γc (IL2RG), JAK3, or IL-21R have revealed that this pathway – activated by IL-21 – is critical for the generation of memory B cells and the establishment of Ag-specific Abs in vivo. Thus, although cytokines such as IL-4, IL-13, IL-10, and BAFF/APRIL are strong B-cell growth and differentiation factors, their function is insufficient to compensate for impaired IL-21/IL-21R signaling in vivo in the setting of generating robust, long-lived Ag-specific Ab, and memory responses. Consequently, IL-21-mediated B-cell activation is a necessary and sufficient step in the generation of protective long-lived humoral immune responses in humans.