Fig. 1
From: The role of autoantibodies in bridging obesity, aging, and immunosenescence
Aging- and obesity-related risk factors contributing to the generation of autoreactive B cells and autoantibodies. A) Autoreactive B cells can be generated throughout the B cell development, from hematopoietic stem cells in the BM to various mature, differentiated B cells. In the BM, central tolerance mechanisms, including receptor editing, clonal deletion, and anergy, reduce the autoreactivity of immature B cells, which resulted mostly from the random V(D)J recombination. In the spleen (shown here) and lymph nodes, clonal deletion or anergy remove transitional B cells (spleen) or naïve B cells that strongly bind self-antigens and B cells lacking the costimulatory signals from CD4 + TH cells or CD4 + TFH cells. However, obesity- and aging-related risk factors, including several hallmarks of aging, promote the release of autoantigens and compromise the self-tolerance, facilitating the generation of autoreactive B cells and augmenting the function of existing autoreactive B cells. B) In various tissues and organs, including the gastrointestinal tract and kidneys, ectopic lymphoid structures, such as TLS, can potentially provide a niche for autoreactive B cells, facilitating their ability to promote local and systemic inflammation. The resulting pro-inflammatory factors and autoantibodies drive tissue damage in multiple organs, further fueling the ongoing inflammation and systemic diseases. ANCA = anti-neutrophil cytoplasm antibody; Abeta = amyloid beta; ASCA = anti-Saccharomyces cerevisiae antibodies; BCR = B cell receptor; BTK = Bruton tyrosine kinase; COL1A1 = collagen 1 A; CSR = class switch recombination; DMD = Dystrophin; FN1 = fibronectin; FYN = tyrosine-protein kinase Fyn; GC = germinal center; GRP78 = Glucose regulated protein 78; GP2 = Glycoprotein 2; HSP60 = Heat shock protein 60; MyHC = Myosin Heavy Chain; OmpC = outer membrane porin C; PLIN1 = Perilipin 1; SASP = senescence-associated secretory phenotype; SC5D = Sterol-C5-desaturase; SHM = somatic hypermutation; TLS = tertiary lymphoid structures; USP4 = Ubiquitin specific protease 4