Mechanism and therapeutic prospects of adipose tissue B lymphocytes in obesity and obesity‑associated metabolic diseases (Review)

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  Figure 1.. Functions of B-cell subsets in adipose tissue. Under physiological conditions, B-1 cells constitute a major population of B cells in adipose tissue and can be further subdivided into B-1a and B-1b subsets. B-1a cells predominantly secrete natural IgM, which recognizes and clears oxidized low-density lipoprotein and produce the anti-inflammatory cytokine IL-10, promoting macrophage polarization toward the M2 phenotype while suppressing M1 activation, thereby exerting anti-inflammatory effects. B-1b cells also mainly secrete IgM, contributing to innate immune defense and the maintenance of tissue homeostasis. Bregs, through IL-10 secretion and cooperation with Tregs, suppress the proportion and effector functions of Th1/Th17 cells, thereby inhibiting inflammatory responses. Under obese conditions, B-2 cells become the predominant B-cell population in adipose tissue and can further differentiate into FOB, MZB and ABCs. Upon antigen stimulation and with the help of Tfh cells, FOB cells enter germinal centers and differentiate into MBCs and PCs, producing IgM or undergoing class-switch recombination. MZB cells rapidly respond to antigenic stimulation and contribute to the production…

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  Figure 2.. Adipose tissue microenvironment promotes B-cell functional reprogramming and regulates metabolic inflammation. Under obese conditions, enhanced lipolysis in adipocytes leads to elevated levels of FFAs, accompanied by increased leptin secretion and the formation of SASP. Leptin acts on B-2 cells via its receptor Ob-Rb, activating mTORC1 as well as the JAK2/STAT3 and p38 MAPK/ERK1/2 signaling pathways, thereby promoting pro-inflammatory activation of B-2 cells. SASP simultaneously activates the JAK/STAT3 and NF-κB pathways, amplifying inflammatory signaling. Moreover, obesity-associated gut dysbiosis and high FFA levels increase LPS levels in adipose tissue. LPS, through the TLR4-MyD88-NF-κB signaling axis, promotes B-2 cell expansion and inflammatory responses. At the same time, B-2 cells increase the synthesis and secretion of CH25H, which inhibits the differentiation and maintenance of IgA+ B cells, further impairing the intestinal IgA barrier. The reduction in IgA+ B cells also promotes B-cell senescence, increasing the proportion of ABCs and the secretion of IgG2c antibodies, thereby exacerbating inflammation. These converging signaling pathways collectively elevate levels of…