A Nonredundant Role for IL-21 Receptor Signaling in Plasma Cell Differentiation and Protective Type 2 Immunity against Gastrointestinal Helminth Infection

Pathogen-specific Ab production following infection with the gut-dwelling roundworm Heligmosomoides polygyrus is critical for protective immunity against reinfection. However, the factors required for productive T cell-B cell interactions in the context of a type 2-dominated immune response are not well defined. In the present study, we identify IL-21R signaling as a critical factor in driving pathogen-specific plasma cell differentiation and protective immunity against H. polygyrus in mice. We show that B cells require direct IL-21R signals to differentiate into CD138(+) plasma cells. In contrast, IL-21R signaling is dispensable for germinal center formation, isotype class switching, and Th2 and T follicular helper cell differentiation. Our studies demonstrate a selective role for IL-21 in plasma cell differentiation in the context of protective antiparasitic type 2 immunity. The Journal of Immunology, 2010, 185: 6138-6145.