@article{6b70bee72fb9499caefe7198962a4cf7,
title = "T-bet+ B cells accumulate in adipose tissue and exacerbate metabolic disorder during obesity",
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.",
keywords = "adipose tissue, B cells, CD11c T-bet B cells, glucose intolerance, IgG2c, inflammation, iNKT cells, metabolic disorder, obesity, type 2 diabetes",
author = "Thomas H{\"a}ggl{\"o}f and Carlo Vanz and Abigail Kumagai and Elizabeth Dudley and Vanessa Ortega and McKenzie Siller and Raksha Parthasarathy and Josh Keegan and Abigail Koenigs and Travis Shute and Leadbetter, {Elizabeth A.}",
note = "Funding Information: We thank L. Lynch (Harvard Medical School/Trinity College Dublin), E. Meffre (Yale School of Medicine), G. Winslow (SUNY Upstate Medical University), and M. Jenkins (University of Minnesota Medical School) for fruitful discussions and kind assistance. We thank the UT Health Flow Cytometry Core and vivarium for essential services and the US NIH Tetramer Core for CD1d-PBS57 tetramers. We are indebted to Dr. Michael Decherd, Kim Arnold, and the patients of the San Antonio Plastic Surgery Institute for essential clinical samples. We thank M. Nussenzweig (Rockefeller University), M. Exley (University of Manchester, UK), M. Mohrs (Trudeau Institute), and M. Brenner (BWH/HMS) for critical mouse strains. This study was supported by the Swedish Research Council (T.H.), NIH R01 AI32798-01A1 (E.A.L.), a Voelcker Fund Young Investigator Award (E.A.L.), and UT Health faculty support (E.A.L.). Funding Information: We thank L. Lynch (Harvard Medical School/Trinity College Dublin), E. Meffre (Yale School of Medicine), G. Winslow (SUNY Upstate Medical University), and M. Jenkins (University of Minnesota Medical School) for fruitful discussions and kind assistance. We thank the UT Health Flow Cytometry Core and vivarium for essential services and the US NIH Tetramer Core for CD1d-PBS57 tetramers. We are indebted to Dr. Michael Decherd, Kim Arnold, and the patients of the San Antonio Plastic Surgery Institute for essential clinical samples. We thank M. Nussenzweig (Rockefeller University), M. Exley (University of Manchester, UK), M. Mohrs (Trudeau Institute), and M. Brenner (BWH/HMS) for critical mouse strains. This study was supported by the Swedish Research Council (T.H.), NIH R01 AI32798-01A1 (E.A.L.), a Voelcker Fund Young Investigator Award (E.A.L.), and UT Health faculty support (E.A.L.). T.H. C.V. and E.A.L. conceived and designed experiments, analyzed and interpreted data, and wrote and edited the manuscript. T.H. C.V. A. Kumagai, J.K. T.S. V.O. M.S. R.P. and A. Koenigs performed experiments. E.A.L. directed the study and secured funding. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = aug,
day = "2",
doi = "10.1016/j.cmet.2022.07.002",
language = "English (US)",
volume = "34",
pages = "1121--1136.e6",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "8",
}