IL-2 secreting T helper cells promote EF B cell maturation via intrinsic regulation of B cell mTOR/AKT/Blimp-1 axis.

SUMMARYB cells are fundamental players in the secretion of antibodies and the establishment of long-term memory-based immunity. Integration of signals from TLRs, BCR stimulation, and T helper cell-derived cytokines can all dictate B cell differentiation and their metabolic state. However, while important components of this interaction have been described, the precise signaling networks and mechanisms regulating B cell fate are not fully understood. Here, we elucidated the role of interleukin-2 (IL-2) in determining early B cell fate decisions and inducing plasma cell reprogramming. Using both in vitro culture systems and in vivo models of immunization, alongside CRISPR-based genome editing of antigen-specific T and B cells, we identify a role for T helper-secreted IL-2 in inducing high expression of Irf4 and Blimp-1 in activated cognate B cells, enhancing plasma cell differentiation. Induction of this cascade promotes their differentiation and drives metabolic reprogramming through the regulation of mTOR/AKT/Blimp-1 axis.