Synthetic auxotrophy reveals metabolic regulation of plasma cell generation, affinity maturation, and cytokine receptor signaling.

Conditional glutaminase (Gls) requirement in mouse B cells is linked to anti-NP antibody responses, but only when glucose uptake or mitochondrial pyruvate import is impaired.

• Why it matters: Understanding how intermediary metabolism shapes plasma cell generation, affinity maturation, and cytokine receptor signaling is key for humoral immunity and autoimmune disease control.
• What they did: Using synthetic auxotrophy, the study restricted glutamine supply and impaired Gls while also blocking either glucose uptake or pyruvate entry into mitochondria, then assessed Ab responses and STAT signaling after IL-21 or interferon stimulation.
• The result: Glutaminase impairment reduced IL-21–driven STAT3 phosphorylation and interferon–driven STAT1 activation, and it linked metabolic pathway collaboration to progressive mitochondrial respiration and plasma cell differentiation.

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