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

Faliti, C. E.; Mesina, M.; Choi, J.; Belanger, S.; Schief, W. R.; Crotty, S.

doi:10.1101/2022.08.19.504576

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bioRxiv · 10.1101/2022.08.19.504576

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

Faliti, C. E.·Mesina, M.·Choi, J.·Belanger, S.·Schief, W. R.·Crotty, S.

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Abstract

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.

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Faliti, C. E., Mesina, M., Choi, J., Belanger, S., Schief, W. R., Crotty, S.. 2022-08-20. IL-2 secreting T helper cells promote EF B cell maturation via intrinsic regulation of B cell mTOR/AKT/Blimp-1 axis.. https://doi.org/10.1101/2022.08.19.504576

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