%A Karnell,Jodi %A Ettinger,Rachel %D 2012 %J Frontiers in Immunology %C %F %G English %K BAFF,BLys,human B cell,IL-21 %Q %R 10.3389/fimmu.2012.00002 %W %L %M %P %7 %8 2012-January-24 %9 Review %+ Dr Rachel Ettinger,MedImmune,1 MedImmune Way,Gaithersburg,20878,MD,United States,ettingerc@medimmune.com %# %! Effect of IL-21 and BAFF on human B cell responses %* %< %T The Interplay of IL-21 and BAFF in the Formation and Maintenance of Human B Cell Memory %U https://www.frontiersin.org/articles/10.3389/fimmu.2012.00002 %V 3 %0 JOURNAL ARTICLE %@ 1664-3224 %X To date, IL-21 stands out as the most influential cytokine for human B cell activation and differentiation. Indeed, when compared to other important B cell tropic cytokines such as IL-2, IL-4, IL-6 and IL-10, IL-21 is clearly the most potent in terms of its ability to influence humoral immune responses in humans. IL-21 has wide reaching actions in determining how B cells will respond to co-stimulation ranging from induction of cell death upon BCR crosslinking to potent induction of class switch recombination and plasma cell differentiation when CD40 molecules are co-engaged. Another crucial B cell factor, exemplified in recent clinical trials, is BAFF/BLys. BAFF plays a critical role in the survival of human B cells and plasma blasts and influences B cell expansion and migration. Recent evidence has shown that IL-21 and BAFF can work in concert to promote and perhaps maintain humoral immunity in humans. Notably, BAFF has the unique ability to substitute for CD40L activities in regard to IL-21-co-stimulation and differentiation of a specific B cell subpopulation located in the human splenic marginal zone. However, and perhaps surprisingly, BAFF signals do not have the capability to override IL-21-driven cell death events when BCR is engaged. In stark contrast, anti-CD40 ligation of B cells co-activated with IL-21 and anti-IgM not only reverses this aforementioned activation-induced cell death, but transforms this death signal into one that drives plasma cell differentiation. Here we will discuss these two critical B cell factors, IL-21 and BAFF, and their distinct and complimentary effects on human B cell responses.