Cambridge Immunology Network

Immune responses in fat-associated lymphoid tissue

Dr Jorge Caamaño explains how inflammation can lead to the formation of fat-associated lymphoid clusters.

Rapid immune responses within the peritoneal and pleural cavities involve innate-like B cell populations known as B-1 cells. These cells are vital for antibody-production in the early fight against infection, they help protect against autoimmunity and contribute to adaptive immunity. They can be found in abundance in areas of adipose tissue within the visceral fat of the peritoneal and pleural cavities that are referred to as fat-associated lymphoid clusters (FALCs). The formation of these clusters can be induced by inflammation1. However, an exact composition, distribution, function and mechanism of FALC development remains unknown.

Characterizing FALCs

Looking at immunofluorescence staining of mouse mesenteric tissues, with antibodies specific for the T cell-specific co-receptor CD4, the hematopoietic marker CD45, immunoglobulin M (IgM) and the common myeloid marker CD11b (integrin αM), Dr Caamaño and his team were able to characterize FALC composition.

FALCs were highly vascularized (as shown by the presence of CD31+ blood vessels) and composed primarily of IgM+ B cells, with low numbers of CD4+ T cells and CD11b+ myeloid cells. Expression of the gene encoding the homeostatic chemokine CXCL13 (Cxcl13) – required for the recruitment of B cells – was more than 100-folder higher in FALCs than in the associated adipose tissue.

FALC function and formation

Immunization of mice with the T cell-independent antigen NP-Ficoll led to the proliferation of B-1 cells in FALCs (as seen by flow cytometry analysis of Ki67, 24 hours after intraperitoneal immunization) along with the presence of IgM- and IgG-producing cells.

Peritoneal inflammation, induced experimentally by zymosan, led to the formation of FALCs greater in size and number than treatment with a control (PBS). This effect was dependent on tumor necrosis factor (TNF) expression on myeloid cells and TNF receptor signaling in stromal cells.

FALC stromal cells expressed high levels of CXCL13 that was crucial for the recruitment and retention of B cells in the clusters. In addition to an inflammatory signal delivered via TNF, FALC formation was triggered by activation of invariant NKT (iNKT) cells that required signaling through IL-4Rα. iNKT cell activity was both necessary and sufficient for FALC formation.

FALCs appear to support B cell differentiation and proliferation and contribute to peritoneal cavity B-1 cell immune responses during inflammation.


FALC formation in response to inflammation is proposed to link innate and adaptive immune responses that support the rapid proliferation of B cells and subsequent antibody secretion within body cavities during events such as infection.

There are still questions over the possible role of FALCs in obesity, the nature of the stromal cells forming parts of the clusters, and possibility that FALCs may in fact be a primitive type of lymphoid tissue – a lymph node predecessor.


1. Bénézech, C. et al. Inflammation-induced formation of fat-associated lymphoid clusters. Nat. Immunol. 16, 819–28 (2015).

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