IL-21 contributes to type 2 memory B cell formation.

Type 2 memory B cells (mBC2), identified in mice as IgG1+CD23+IL-4Rα+CD38+ B cells, which require IL-4 for genesis, are precursors for IgE plasma cells (PC) and considered key in allergy. While IL-21 is critical for normal mBC differentiation, its involvement in mBC2 formation is unknown. Here, we show that although IL-21R-deficient (IL-21R-/-) mice immunized with ovalbumin generated ovalbumin-specific mBC2, their abundances were lower than in controls one-week post-immunization. This deficit was associated with the accumulation of pre-prememory GC B cells and corresponding deficiencies in pre-memory B cell exit, suggesting a defect in memory differentiation. Germinal centers waned rapidly in IL-21R-/- mice and subsequently mBC2 numbers diminished, and IgG1 PC genesis was suppressed. These data show that IL-21 is required for normal mBC2 formation, arguing against the use of IL-21 as a pan-allergy suppressor.