Inflammation-induced formation of fat-associated lymphoid clusters

Bénézech, Cécile and Luu, Nguyet-Thin and Walker, Jennifer A and Kruglov, Andrei A and Loo, Yunhua and Nakamura, Kyoko and Zhang, Yang and Nayar, Saba and Jones, Lucy H and Flores-Langarica, Adriana and McIntosh, Alistair and Marshall, Jennifer and Barone, Francesca and Besra, Gurdyal and Miles, Katherine and Allen, Judith E and Gray, Mohini and Kollias, George and Cunningham, Adam F and Withers, David R and Toellner, Kai Michael and Jones, Nick D and Veldhoen, Marc and Nedospasov, Sergei A and McKenzie, Andrew N J and Caamaño, Jorge H (2015) Inflammation-induced formation of fat-associated lymphoid clusters. Nature Immunology, 16 (8). pp. 819-828. ISSN 1529-2908

Abstract

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.