Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation

Abstract

Distinct B cell populations, designated regulatory B (B) cells, are known to restrain immune responses associated with autoimmune diseases. Additionally, obesity is known to induce local inflammation within adipose tissue that contributes to systemic metabolic abnormalities, but the underlying mechanisms that modulate adipose inflammation remain poorly understood. We identified B cells that produce interleukin-10 constitutively within adipose tissue. B cell-specific Il10 deletion enhanced adipose inflammation and insulin resistance in diet-induced obese mice, whereas adoptive transfer of adipose tissue B cells ameliorated those effects. Adipose environmental factors, including CXCL12 and free fatty acids, support B cell function, and B cell fraction and function were reduced in adipose tissue from obese mice and humans. Our findings indicate that adipose tissue B cells are a naturally occurring regulatory B cell subset that maintains homeostasis within adipose tissue and that B cell dysfunction contributes pivotally to the progression of adipose tissue inflammation in obesity.

Spleen supports a pool of innate-like B cells in white adipose tissue that protects against obesity-associated insulin resistance

“…We show here that a substantial number of B cells with a surface phenotype resembling innate-like B-1a and regulatory B10 B cells (12,16,29) but distinct from recently identified "adipose natural regulatory B cells" (19) populate VAT under steady-state conditions. Similar to their counterparts in spleen and PerC, these cells in VAT spontaneously produce IgM antibodies and constitute the majority of IL-10-competent B cells at this anatomic location.…”

“…nate response activator (IRA) B cells have been identified in lymphoid organs and in peritoneal cavity (PerC) of mice (12,(14)(15)(16)(19)(20)(21). These innate-like B-cell subsets share several phenotypic and functional characteristics but also display important differences.…”

“…1A), a marker that distinguishes B-1a from B-1b B cells (12) and is lacking in adipose natural regulatory B cells (19). These TCRβ −…”

Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis

“…Flow cytometric analyses of SVF were performed as described 43,44 . In brief, the epididymal fat tissue was collected and cut into small pieces and incubated for 20 min in collagenase solution (2 mg ml À 1 of collagenase type 2 (Worthington, Lakewood, NJ)) with gentle shaking.…”

Eicosapentaenoic and docosahexaenoic acid ethyl esters differentially enhance B-cell activity in murine obesity

“…Natural IgM increases phagocytosis of apoptotic cells in the marginal zone to increase IL-10-secreting B cells ( 24,36 ). Furthermore, improving IL-10 secretion in the adipose is of particular signifi cance because IL-10-secreting B cells improve insulin sensitivity in obesity ( 37 ).…”