B‐1 lymphocytes in adipose tissue as innate modulators of inflammation linked to cardiometabolic disease

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  Figure 1:. Schematic of B cell subtype development. (A) According to the lineage model, B-1 cells and B-2 cells originate from different progenitors, with B-1 cell (B-1a and B-1b) originating from the fetal liver and not the bone marrow. In the induced differentiation model, B-1 and B-2 cells originate from the same precursor in the bone marrow, but differentiate into B-1 or B-2 cells depending on the strength of the B cell receptor signal and environmental cues received by the progenitor cell. Immature B-2 cells exit the bone marrow as transitional 1 (T1) cells and migrate to secondary lymphoid organs, such as spleen. (B) In the spleen, the T1 cells differentiate into transitional 2 (T2) cells. Based on the intensity of the signal from the B cell receptors and the availability of BAFF, they differentiate into marginal zone B (BMZ) or follicular (BFO) B cells. BMZ cells migrate to the marginal zone, where they secrete polyreactive IgGs and IgMs to antigens found in the red pulp. B-1 cells, irrespective of their origin, also migrate to the spleen and secrete polyreactive IgMs against encountered antigens. BFO localizes in the follicles of the spleen, and upon activation by antigens presented…

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  Figure 2:. Obesity-induced inflammation in the omentum. (A) Localization of FALCs in the omentum. (B) High levels of IL-33 in FALC in mesentery and omentum promote Id3-mediated IL-5 production. IL-5 is a key mitogen for expansion of B-1a cells, leading to increased number of B-1a cells and the production of natural IgM antibodies (such as E06), which bind to oxidized phospholipids (PL), such as low-density lipoprotein (LDL). M1 macrophages take up oxidized LDL, become foamy macrophages, and produce increased amounts of the proinflammatory cytokines TNF-α and IFN-γ. However, binding of EO6 to oxidized LDL inhibits this process, thus decreasing the amounts of proinflammatory cytokines. Similar to B-1a cells, B-1b cells can secrete EO6 antibodies and suppress inflammation in the omentum.

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  Figure 3:. B-1 cells in PVAT can dampen local inflammation to limit atherosclerotic lesion formation. Foam cells formed by the uptake of oxidized LDL by M1 macrophages promotes inflammation in the atherosclerotic plaques. This inflammation can be partly suppressed by EO6 antibodies secreted by B-1a and B-1b cells that binds to oxidized LDL. nILC2 cells also localized in the PVAT and supports B-1a cell expansion. Both the B-1a and B-1b cells use the CCR6 receptor to migrate to the PVAT.