Figure 1. B cells and adipose tissue.

Fat-associated lymphoid clusters (FALC), omental milky spots (MS), and lean fat in general (blue boxes) have features favoring immune regulation. IL5 production by FALC sustains self-renewal of B1 B cells. B cells in this subset may produce IL10 and exert regulatory activity (Breg) [46,47]. B1 B cells also produce IgM, known to provide protection against influenza virus and also against bacteria such as Borrelia hermsii and S. pneumoniae. B1 cell-derived IgM against oxLDL may prevent this metabolite from exacerbating vascular atherosclerotic lesions. Omental and peritoneal B1 B cells also contribute to gut IgA production [45], important for oral tolerance and microbiota homeostasis. Incidentally, lean fat is enriched in TGFβ-producing regulatory T cells (Treg), which may provide this critical factor for IgA class switching. A Th2 bias in lean fat, including type 2 cytokine production by FALC cells, likely favors IgG1 production by conventional, B2 B lymphocytes. IgG1 against oral antigens contributes to oral tolerance in mice. Additionally, IgG1 against oxLDL may prevent or dampen vascular lesion formation by engaging the inhibitory Fc receptor (Fcγ RIIB) [83]. Th2 cytokine influence of B2 B cells may also promote IgE production favoring parasite expulsion. By contrast, obese fat (red boxes) tends to be in a pro-inflammatory state favoring exacerbation and/or initiation of autoimmune pathologies. This state includes a paucity of Tregs and a Th1 bias that may cooperate with B2 B cells to generate IgG2a/c. IgG2a/c against oral antigens in mice may contribute to poor oral tolerance (e.g., by complement fixation). IgG2a/c immune complexes with modified LDL may engage activating FcR (e.g., on macrophages) and exacerbate atherosclerotic lesions.