{
  "abstract": "The proliferation and development of activated B lymphocytes into antibody (Ab)-secreting plasma cells are critical determinants of humoral immunity and sustain certain autoimmune diseases. Specific pathways and substrate supplies in intermediary metabolism influence lymphocyte differentiation and function. We now show that although stringent restriction of glutamine supply decreases B cell proliferation and differentiation into plasma cells, glutaminolysis – a major metabolic use of this amino acid – was only conditionally crucial in B cells and the Ab responses derived from them. Gls, the gene encoding the main glutaminase of lymphocytes, promoted anti-NP Ab responses at the primary and recall phases if either glucose uptake into mouse B cells or pyruvate into their mitochondria was also impaired. Otherwise, it was dispensable. This synthetic auxotrophy, that is, the conditional requirement of glutaminase for processes in addition to survival, involved supporting progressive expansion of mitochondrial respiration followed by plasma cell differentiation. Surprisingly, impairment of glutaminase and the mitochondrial pyruvate channel decreased IL-21 stimulation of STAT3 phosphorylation as well as interferon stimulation of STAT1 activation. Together, our findings establish a powerful collaboration of metabolic pathways in programming increased respiration and the development of Ab-secreting cells, but also reveal modulation of cytokine receptor signaling by metabolism.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Microbiology and Immunology, Molecular Pathogenesis Division, Vanderbilt University Medical Center, Nashville, United States",
    "Cancer Biology Program, Vanderbilt University, Nashville, United States",
    "Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, United States",
    "Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, United States",
    "Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, United States",
    "Vanderbilt Center for Infection, Inflammation, Immunology (VI4), Vanderbilt University Medical Center, Nashville, United States",
    "Department of Medicine, Rheumatology and Immunology Division, Vanderbilt University Medical Center, Nashville, United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sung Hoon Cho",
      "orcid": "0000-0002-6463-4032"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shawna K Brookens"
    },
    {
      "affs": [
        0
      ],
      "name": "Ariel L Raybuck"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaylor Meyer"
    },
    {
      "affs": [
        0
      ],
      "name": "Yeeun Paik",
      "orcid": "0009-0004-9369-2890"
    },
    {
      "affs": [
        0
      ],
      "name": "Jennie Hamilton"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingxin Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Karel Kalecky"
    },
    {
      "affs": [
        0
      ],
      "name": "Chloe Park"
    },
    {
      "affs": [
        0
      ],
      "name": "Juyeon Lim"
    },
    {
      "affs": [
        3
      ],
      "name": "Sakeenah L Hicks"
    },
    {
      "affs": [
        0
      ],
      "name": "John Karijolich"
    },
    {
      "affs": [
        2
      ],
      "name": "Teodoro H Bottiglieri"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Jeffrey C Rathmell",
      "orcid": "0000-0002-4106-3396"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Denis Mogilenko",
      "orcid": "0000-0001-5427-5243"
    },
    {
      "affs": [
        3
      ],
      "name": "Christopher D Scharer",
      "orcid": "0000-0001-7716-8504"
    },
    {
      "affs": [
        0,
        1,
        4,
        5,
        6
      ],
      "name": "Mark R Boothby",
      "orcid": "0000-0003-2593-8276"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b9h5w47djwpcd.bib",
  "cited_by": 0,
  "doi": "10.7554/elife.107627",
  "fulltext_url": "https://elifesciences.org/articles/107627",
  "id": "b9h5w47djwpcd",
  "issns": [
    "2050-084X"
  ],
  "landing_url": "https://elifesciences.org/articles/107627",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "elife",
      "immunology-inflammation"
    ],
    [
      "heading",
      "Immunology and Inflammation"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
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  "openalex": "W4413281657",
  "pdf_url": "https://cdn.elifesciences.org/articles/107627/elife-107627-v1.pdf",
  "pmcid": "PMC13719169",
  "pmid": "42956059",
  "published": "2026-10-29",
  "publisher": "eLife Sciences Publications",
  "ris": "https://research.draconitic.com/paper/b9h5w47djwpcd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:25Z",
      "native_id": "107627",
      "source": "elife",
      "url": "https://elifesciences.org/articles/107627"
    },
    {
      "first_seen": "2026-10-31T00:20:39Z",
      "native_id": "MED:42956059",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42956059"
    },
    {
      "first_seen": "2026-11-02T12:23:03Z",
      "native_id": "PMC13719169",
      "source": "pmc",
      "url": "https://doi.org/10.7554/elife.107627"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "elife:immunology-inflammation",
      "subfield": "immunology"
    }
  ],
  "title": "Synthetic auxotrophy reveals metabolic regulation of plasma cell generation, affinity maturation, and cytokine receptor signaling",
  "title_text": "Synthetic auxotrophy reveals metabolic regulation of plasma cell generation, affinity maturation, and cytokine receptor signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:23:03Z",
  "url": "https://research.draconitic.com/paper/b9h5w47djwpcd",
  "venue": "eLife",
  "versions": []
}