Fat-associated lymphoid clusters (FALCs) are a type of lymphoid tissue associated with visceral fat. Here we found that the distribution of FALCs was heterogeneous, with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 cells in the peritoneal cavity through high expression of the chemokine CXCL13, and they supported B cell proliferation and germinal center differentiation during peritoneal immunological challenges. FALC formation was induced by inflammation, which triggered the recruitment of myeloid cells that expressed tumor-necrosis factor (TNF) necessary for signaling via the TNF receptors in stromal cells. Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. Thus, FALCs supported and coordinated the activation of innate B cells and T cells during serosal immune responses.

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We thank the personnel of the Biomedical Services Unit of the University of Birmingham for animal colony care; E. Jenkinson for support; G. Anderson, P. Lane, and A. Rot for comments on the manuscript; C. Buckley for facilitating animal procedures; R. Bird for cell sorting; K. Pfeffer (Heinrich Heine University) for Ltbr−/− mice; G. Eberl (Institut Pasteur) for tissues from germ-free mice; D. Finke (University of Basel) for tissues from Cxcr5−/− mice; A. Diefenback (University of Mainz) for tissues from Id2CreErt2/+Gt(ROSA)26SorYFP/+Gata3f/f mice; and the US National Institutes of Health Tetramer Facility for CD1d-PBS-57 loaded tetramers. Supported by the European Union Framework Programme 7 integrated project INFLACARE (J.H.C.); the Biotechnology and Biological Sciences Research Council (BB/K004900/1 to J.H.C.) and the College of Medical and Dental Sciences of the University of Birmingham (J.H.C.); the American Asthma Foundation, the UK Medical Research Council and the Wellcome Trust (100963/Z/13/Z) for work in the A. McKenzie laboratory; the Biotechnology and Biological Sciences Research Council institute synergy programme, the European Research Council (280307) and the Agency for Science, Technology and Research (to Y.L.) for work in the M. Veldhoen laboratory; Deutsche Forschungsgemeinschaf (NE1466/2-1), the Russian Science Foundation (14-50-00060) and the Russian Foundation for Basic Research (13-04-40268 to A.A.K.) for work in the S. Nedospasov laboratory; the European Research Council (340217-MCs_inTEST) for work in the G. Kollias laboratory; the Medical Research Council (S.N.); the UK Medical Research Council (MRC/K01207X/1 to L.H.J.); and the Lifelong Health and Wellbeing cross council initiative (Topjabs G1001390 for K.M.T., Y.Z. and J.M.).

Author information

Author notes

    • Cécile Bénézech
    •  & Lucy H Jones

    Present address: BHF/UoE Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK.

    • Nguyet-Thin Luu
    •  & Jennifer A Walker

    These authors contributed equally to this work.


  1. School of Immunity and Infection, IBR-MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

    • Cécile Bénézech
    • , Nguyet-Thin Luu
    • , Kyoko Nakamura
    • , Yang Zhang
    • , Saba Nayar
    • , Adriana Flores-Langarica
    • , Alistair McIntosh
    • , Jennifer Marshall
    • , Francesca Barone
    • , Adam F Cunningham
    • , David R Withers
    • , Kai Michael Toellner
    • , Nick D Jones
    •  & Jorge H Caamaño
  2. MRC Laboratory of Molecular Biology, Cambridge, UK.

    • Jennifer A Walker
    •  & Andrew N J McKenzie
  3. Inflammation Biology, German Rheumatism Research Center, Leibniz Institute, Berlin, Germany.

    • Andrei A Kruglov
    •  & Sergei A Nedospasov
  4. Engelhardt Institute of Molecular Biology, Moscow, Russia.

    • Andrei A Kruglov
    •  & Sergei A Nedospasov
  5. Lomonosov Moscow State University, Moscow, Russia.

    • Andrei A Kruglov
    •  & Sergei A Nedospasov
  6. Lymphocyte Signalling and Development Programme, The Babraham Institute, Cambridge, UK.

    • Yunhua Loo
    •  & Marc Veldhoen
  7. Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK.

    • Lucy H Jones
    •  & Judith E Allen
  8. College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK.

    • Gurdyal Besra
  9. Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.

    • Katherine Miles
    •  & Mohini Gray
  10. Division of Immunology, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.

    • George Kollias
  11. Departament of Experimental Physiology, National and Kapodistrian University of Athens, Athens, Greece.

    • George Kollias


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C.B., N.-T.L., J.A.W., A.A.K., Y.L., K.N., Y.Z., S.N., L.H.J. and J.H.C. designed and performed the research and collected and analyzed the data; A.F.-L., A.M., J.M., F.B., G.B., K.M., J.E.A., M.G., G.K., A.F.C., D.R.W., K.M.T., N.D.J., M.V., S.A.N. and A.N.J.M. facilitated the research; and C.B. and J.H.C. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Cécile Bénézech or Jorge H Caamaño.

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