Interleukin-10 expressing B lineage cells in visceral adipose tissue protect against aging-related insulin resistance and extend lifespan.

IL-10 expressing B lineage (B-10) cells are greatly expanded in aged visceral adipose tissue (VAT) in both humans and mice.

• Expansion of B-10 cells was observed in aged VAT in human subjects as well as in mouse models.
• B-10 cells were identified as the primary source of IL-10 in aged VAT.
• This expansion was specific to the VAT microenvironment.

B cell-specific knockout of IL-10 exaggerated aging-related inflammation and insulin resistance and reduced lifespan.

• Mice with B cell-specific IL-10 knockout showed worsened aging-related systemic inflammation compared to controls.
• Insulin resistance was exaggerated in B cell-specific IL-10 knockout mice during aging.
• Lifespan was reduced in B cell-specific IL-10 knockout mice.
• These phenotypes could be partially recovered via adoptive transfer of B-10 cells from wild-type mice.

Adoptive transfer of B-10 cells from wild-type mice partially recovered the exaggerated aging phenotypes caused by B cell-specific IL-10 knockout.

• Transfer of wild-type B-10 cells into B cell-specific IL-10 knockout mice partially ameliorated aging-related inflammation.
• Insulin resistance was partially rescued following adoptive transfer of B-10 cells.
• The partial recovery indicates that B-10 cell-derived IL-10 is a key mediator of protection.

The aged VAT microenvironment enhanced both IL-10 secretion and proliferation of B-10 cells.

• Exposure to the aged VAT microenvironment increased IL-10 secretion by B-10 cells.
• Proliferation of B-10 cells was also promoted by the aged VAT microenvironment.
• These effects suggest a local tissue-driven regulatory mechanism.

BAFF levels are increased in aged VAT and mediate the proliferation and expansion of B-10 cells.

• BAFF was identified as elevated in aged VAT compared to younger VAT.
• Knockdown of BAFF in VAT compromised the aging-related expansion of B-10 cells.
• BAFF was specifically implicated in driving B-10 cell proliferation rather than other B cell populations.

VAT-specific overexpression of BAFF promoted B-10 cell expansion, improved aging-related inflammation and insulin resistance, and prolonged lifespan.

• Targeted overexpression of BAFF in VAT led to increased B-10 cell numbers in aged mice.
• Aging-related inflammation was improved in mice with VAT-specific BAFF overexpression.
• Insulin resistance was ameliorated in these mice.
• Lifespan was prolonged in mice with VAT-specific BAFF overexpression, establishing a functional link between local BAFF signaling, B-10 cells, and longevity.