| First Author | Shen L | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 2 | Pages | 593-603 |
| PubMed ID | 25249575 | Mgi Jnum | J:250298 |
| Mgi Id | MGI:5922074 | Doi | 10.2337/db14-0554 |
| Citation | Shen L, et al. (2015) B-1a lymphocytes attenuate insulin resistance. Diabetes 64(2):593-603 |
| abstractText | Obesity-associated insulin resistance, a common precursor of type 2 diabetes, is characterized by chronic inflammation of tissues, including visceral adipose tissue (VAT). Here we show that B-1a cells, a subpopulation of B lymphocytes, are novel and important regulators of this process. B-1a cells are reduced in frequency in obese high-fat diet (HFD)-fed mice, and EGFP interleukin-10 (IL-10) reporter mice show marked reductions in anti-inflammatory IL-10 production by B cells in vivo during obesity. In VAT, B-1a cells are the dominant producers of B cell-derived IL-10, contributing nearly half of the expressed IL-10 in vivo. Adoptive transfer of B-1a cells into HFD-fed B cell-deficient mice rapidly improves insulin resistance and glucose tolerance through IL-10 and polyclonal IgM-dependent mechanisms, whereas transfer of B-2 cells worsens metabolic disease. Genetic knockdown of B cell-activating factor (BAFF) in HFD-fed mice or treatment with a B-2 cell-depleting, B-1a cell-sparing anti-BAFF antibody attenuates insulin resistance. These findings establish B-1a cells as a new class of immune regulators that maintain metabolic homeostasis and suggest manipulation of these cells as a potential therapy for insulin resistance. |
