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Significance The precise regulation of antibody responses is central to the efficacy of vaccines and to our handling of microbes and infections. Antibody quality is enhanced in germinal center reactions, and this microstructure in tissue has to cope with limited oxygen. This work shows that a pair of hypoxia-inducible factor (HIF) proteins, gene regulators that respond to low oxygen but also are induced by T cell activation, must be expressed in helper T cells in order for immunization to yield a good antibody response. The evidence favors a multifactorial mechanism: HIFs shift the balance between follicular regulatory and helper T cells but also regulate metabolism, numbers of follicular helpers, and molecules they express to promote antibody production.

Hypoxia-inducible factors in CD4+T cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity

Hypoxia-inducible factors in CD4⁺T cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity