T-bet+ B cells accumulate in adipose tissue and exacerbate metabolic disorder during obesity

Thomas Hägglöf, Carlo Vanz, Abigail Kumagai, Elizabeth Dudley, Vanessa Ortega, McKenzie Siller, Raksha Parthasarathy, Josh Keegan, Abigail Koenigs, Travis Shute, Elizabeth A. Leadbetter

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Obesity is accompanied by inflammation in adipose tissue, impaired glucose tolerance, and changes in adipose leukocyte populations. These studies of adipose tissue from humans and mice revealed that increased frequencies of T-bet+ B cells in adipose tissue depend on invariant NKT cells and correlate with weight gain during obesity. Transfer of B cells enriched for T-bet+ cells exacerbates metabolic disorder in obesity, while ablation of Tbx21 specifically in B cells reduces serum IgG2c levels, inflammatory cytokines, and inflammatory macrophages in adipose tissue, ameliorating metabolic symptoms. Furthermore, transfer of serum or purified IgG from HFD mice restores metabolic disease in T-bet+ B cell-deficient mice, confirming T-bet+ B cell-derived IgG as a key mediator of inflammation during obesity. Together, these findings reveal an important pathological role for T-bet+ B cells that should inform future immunotherapy design in type 2 diabetes and other inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)1121-1136.e6
JournalCell Metabolism
Volume34
Issue number8
DOIs
StatePublished - Aug 2 2022

Keywords

  • adipose tissue
  • B cells
  • CD11c T-bet B cells
  • glucose intolerance
  • IgG2c
  • inflammation
  • iNKT cells
  • metabolic disorder
  • obesity
  • type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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