Cellular and Molecular Life Sciences

, Volume 71, Issue 6, pp 1033–1043 | Cite as

B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance

  • Daniel A. Winer
  • Shawn Winer
  • Melissa H. Y. Chng
  • Lei Shen
  • Edgar G. EnglemanEmail author


Obesity-related insulin resistance is a chronic inflammatory condition that often gives rise to type 2 diabetes (T2D). Much evidence supports a role for pro-inflammatory T cells and macrophages in promoting local inflammation in tissues such as visceral adipose tissue (VAT) leading to insulin resistance. More recently, B cells have emerged as an additional critical player in orchestrating these processes. B cells infiltrate VAT and display functional and phenotypic changes in response to diet-induced obesity. B cells contribute to insulin resistance by presenting antigens to T cells, secreting inflammatory cytokines, and producing pathogenic antibodies. B cell manipulation represents a novel approach to the treatment of obesity-related insulin resistance and potentially to the prevention of T2D. This review summarizes the roles of B cells in governing VAT inflammation and the mechanisms by which these cells contribute to altered glucose homeostasis in insulin resistance.


Insulin resistance Type 2 diabetes B lymphocytes Inflammation Autoimmunity Macrophages T cells 



Type 2 diabetes


Visceral adipose tissues


Fat-associated lymphoid cluster


Oxidized low-density lipoprotein


Class switch recombination


Somatic hypermutation


High-fat diet


B cell receptor


Crown-like structure


Diet-induced obese


Golgi SNAP receptor complex member 1


Glial fibrillary acidic protein


B-cell activating factor



This work was supported in part by NIH grant 1R01DK096038 (EE), CIHR Grant 119414 (DW), and CDA grants, OG-3-12-3844 (DW) and CS-5-12-3886 (DW).


  1. 1.
    Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC (2010) Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med 362:485–493PubMedCentralPubMedGoogle Scholar
  2. 2.
    Johnson AM, Olefsky JM (2013) The origins and drivers of insulin resistance. Cell 152:673–684PubMedGoogle Scholar
  3. 3.
    Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedCentralPubMedGoogle Scholar
  4. 4.
    Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedCentralPubMedGoogle Scholar
  5. 5.
    Winer S, Winer DA (2012) The adaptive immune system as a fundamental regulator of adipose tissue inflammation and insulin resistance. Immunol Cell Biol 90:755–762PubMedGoogle Scholar
  6. 6.
    Talukdar S, da Oh Y, Bandyopadhyay G et al (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18:1407–1412PubMedCentralPubMedGoogle Scholar
  7. 7.
    Ozcan U, Cao Q, Yilmaz E et al (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457–461PubMedGoogle Scholar
  8. 8.
    Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246PubMedGoogle Scholar
  9. 9.
    Odegaard JI, Chawla A (2013) Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science 339:172–177PubMedCentralPubMedGoogle Scholar
  10. 10.
    Nishimura S, Manabe I, Nagasaki M et al (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914–920PubMedGoogle Scholar
  11. 11.
    Winer S, Chan Y, Paltser G et al (2009) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15:921–929PubMedCentralPubMedGoogle Scholar
  12. 12.
    Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184PubMedCentralPubMedGoogle Scholar
  13. 13.
    Wu D, Molofsky AB, Liang HE et al (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–247PubMedCentralPubMedGoogle Scholar
  14. 14.
    Feuerer M, Herrero L, Cipolletta D et al (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939PubMedCentralPubMedGoogle Scholar
  15. 15.
    Molofsky AB, Nussbaum JC, Liang HE et al (2013) Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210:535–549PubMedCentralPubMedGoogle Scholar
  16. 16.
    Lynch L, Nowak M, Varghese B et al (2012) Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37:574–587PubMedGoogle Scholar
  17. 17.
    Yanaba K, Bouaziz JD, Matsushita T, Magro CM, St Clair EW, Tedder TF (2008) B-lymphocyte contributions to human autoimmune disease. Immunol Rev 223:284–299PubMedGoogle Scholar
  18. 18.
    Marino E, Grey ST (2012) B cells as effectors and regulators of autoimmunity. Autoimmunity 45:377–387PubMedGoogle Scholar
  19. 19.
    Duffaut C, Galitzky J, Lafontan M, Bouloumie A (2009) Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun 384:482–485PubMedGoogle Scholar
  20. 20.
    Winer DA, Winer S, Shen L et al (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17:610–617PubMedCentralPubMedGoogle Scholar
  21. 21.
    Defuria J, Belkina AC, Jagannathan-Bogdan M et al (2013) B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci USA 110:5133–5138PubMedGoogle Scholar
  22. 22.
    Kaminski DA, Randall TD (2010) Adaptive immunity and adipose tissue biology. Trends Immunol 31:384–390PubMedCentralPubMedGoogle Scholar
  23. 23.
    Haas KM, Poe JC, Steeber DA, Tedder TF (2005) B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. Immunity 23:7–18PubMedGoogle Scholar
  24. 24.
    Cui L, Johkura K, Liang Y et al (2002) Biodefense function of omental milky spots through cell adhesion molecules and leukocyte proliferation. Cell Tissue Res 310:321–330PubMedGoogle Scholar
  25. 25.
    Rangel-Moreno J, Moyron-Quiroz JE, Carragher DM et al (2009) Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens. Immunity 30:731–743PubMedCentralPubMedGoogle Scholar
  26. 26.
    Moro K, Yamada T, Tanabe M et al (2010) Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463:540–544PubMedGoogle Scholar
  27. 27.
    Ha SA, Tsuji M, Suzuki K et al (2006) Regulation of B1 cell migration by signals through Toll-like receptors. J Exp Med 203:2541–2550PubMedCentralPubMedGoogle Scholar
  28. 28.
    Choi YS, Baumgarth N (2008) Dual role for B-1a cells in immunity to influenza virus infection. J Exp Med 205:3053–3064PubMedCentralPubMedGoogle Scholar
  29. 29.
    Morris DL, Cho KW, Delproposto JL et al (2013) Adipose tissue macrophages function as antigen-presenting cells and regulate adipose tissue CD4+ T cells in mice. Diabetes 62:2762–2772PubMedGoogle Scholar
  30. 30.
    Martin F, Kearney JF (2001) B1 cells: similarities and differences with other B cell subsets. Curr Opin Immunol 13:195–201PubMedGoogle Scholar
  31. 31.
    Kunisawa J, Kurashima Y, Gohda M et al (2007) Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production. Blood 109:3749–3756PubMedGoogle Scholar
  32. 32.
    Kearney JF (2000) Immune recognition of OxLDL in atherosclerosis. J Clin Invest 105:1683–1685PubMedCentralPubMedGoogle Scholar
  33. 33.
    Binder CJ, Silverman GJ (2005) Natural antibodies and the autoimmunity of atherosclerosis. Springer Semin Immunopathol 26:385–404PubMedGoogle Scholar
  34. 34.
    Ait-Oufella H, Herbin O, Bouaziz JD et al (2010) B cell depletion reduces the development of atherosclerosis in mice. J Exp Med 207:1579–1587PubMedCentralPubMedGoogle Scholar
  35. 35.
    Kyaw T, Tay C, Khan A et al (2010) Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis. J Immunol 185:4410–4419PubMedGoogle Scholar
  36. 36.
    Mauri C, Ehrenstein MR (2008) The ‘short’ history of regulatory B cells. Trends Immunol 29:34–40PubMedGoogle Scholar
  37. 37.
    Griffin DO, Holodick NE, Rothstein TL (2011) Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+ CD27+CD43+ CD70. J Exp Med 208:67–80PubMedCentralPubMedGoogle Scholar
  38. 38.
    Allman D, Pillai S (2008) Peripheral B cell subsets. Curr Opin Immunol 20:149–157PubMedCentralPubMedGoogle Scholar
  39. 39.
    Lund FE (2008) Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol 20:332–338PubMedCentralPubMedGoogle Scholar
  40. 40.
    Ruprecht CR, Lanzavecchia A (2006) Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur J Immunol 36:810–816PubMedGoogle Scholar
  41. 41.
    LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112:1570–1580PubMedGoogle Scholar
  42. 42.
    Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553–563PubMedGoogle Scholar
  43. 43.
    Yoshida T, Mei H, Dorner T et al (2010) Memory B and memory plasma cells. Immunol Rev 237:117–139PubMedGoogle Scholar
  44. 44.
    Mauri C, Bosma A (2012) Immune regulatory function of B cells. Annu Rev Immunol 30:221–241PubMedGoogle Scholar
  45. 45.
    Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF (2008) A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28:639–650PubMedGoogle Scholar
  46. 46.
    Yoshizaki A, Miyagaki T, DiLillo DJ et al (2012) Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 491:264–268PubMedCentralPubMedGoogle Scholar
  47. 47.
    Melchers F (2005) The pre-B-cell receptor: selector of fitting immunoglobulin heavy chains for the B-cell repertoire. Nat Rev Immunol 5:578–584PubMedGoogle Scholar
  48. 48.
    Lam KP, Kuhn R, Rajewsky K (1997) In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90:1073–1083PubMedGoogle Scholar
  49. 49.
    Trottier MD, Naaz A, Li Y, Fraker PJ (2012) Enhancement of hematopoiesis and lymphopoiesis in diet-induced obese mice. Proc Natl Acad Sci USA 109:7622–7629PubMedGoogle Scholar
  50. 50.
    Claycombe K, King LE, Fraker PJ (2008) A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci USA 105:2017–2021PubMedGoogle Scholar
  51. 51.
    Chan ME, Adler BJ, Green DE, Rubin CT (2012) Bone structure and B-cell populations, crippled by obesity, are partially rescued by brief daily exposure to low-magnitude mechanical signals. FASEB J: Off Publ Fed Am Soc Exp Biol 26:4855–4863Google Scholar
  52. 52.
    Elgazar-Carmon V, Rudich A, Hadad N, Levy R (2008) Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res 49:1894–1903PubMedGoogle Scholar
  53. 53.
    Nguyen MT, Favelyukis S, Nguyen AK et al (2007) A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 282:35279–35292PubMedGoogle Scholar
  54. 54.
    Duddy M, Niino M, Adatia F et al (2007) Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol 178:6092–6099PubMedGoogle Scholar
  55. 55.
    Mauri C, Gray D, Mushtaq N, Londei M (2003) Prevention of arthritis by interleukin 10-producing B cells. J Exp Med 197:489–501PubMedCentralPubMedGoogle Scholar
  56. 56.
    Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF (2008) Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest 118:3420–3430PubMedCentralPubMedGoogle Scholar
  57. 57.
    Hong EG, Ko HJ, Cho YR et al (2009) Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 58:2525–2535PubMedGoogle Scholar
  58. 58.
    Kowalski GM, Nicholls HT, Risis S et al (2011) Deficiency of haematopoietic-cell-derived IL-10 does not exacerbate high-fat-diet-induced inflammation or insulin resistance in mice. Diabetologia 54:888–899PubMedGoogle Scholar
  59. 59.
    van Exel E, Gussekloo J, de Craen AJ, Frolich M, Bootsma-Van Der Wiel A, Westendorp RG (2002) Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-plus study. Diabetes 51:1088–1092PubMedGoogle Scholar
  60. 60.
    Jagannathan M, McDonnell M, Liang Y et al (2010) Toll-like receptors regulate B cell cytokine production in patients with diabetes. Diabetologia 53:1461–1471PubMedCentralPubMedGoogle Scholar
  61. 61.
    Jagannathan-Bogdan M, McDonnell ME, Shin H et al (2011) Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J Immunol 186:1162–1172PubMedCentralPubMedGoogle Scholar
  62. 62.
    Azar Sharabiani MT, Vermeulen R, Scoccianti C et al (2011) Immunologic profile of excessive body weight. Biomarkers 16:243–251Google Scholar
  63. 63.
    Papathanassoglou E, El-Haschimi K, Li XC, Matarese G, Strom T, Mantzoros C (2006) Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high-fat diet in mice. J Immunol 176:7745–7752PubMedGoogle Scholar
  64. 64.
    Agrawal S, Gollapudi S, Su H, Gupta S (2011) Leptin activates human B cells to secrete TNF-alpha, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway. J Clin Immunol 31:472–478PubMedCentralPubMedGoogle Scholar
  65. 65.
    Lam QL, Wang S, Ko OK, Kincade PW, Lu L (2010) Leptin signaling maintains B-cell homeostasis via induction of Bcl-2 and Cyclin D1. Proc Natl Acad Sci USA 107:13812–13817PubMedGoogle Scholar
  66. 66.
    Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116:3015–3025PubMedCentralPubMedGoogle Scholar
  67. 67.
    DiLillo DJ, Yanaba K, Tedder TF (2010) B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice. J Immunol 184:4006–4016PubMedCentralPubMedGoogle Scholar
  68. 68.
    Bouaziz JD, Yanaba K, Venturi GM et al (2007) Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice. Proc Natl Acad Sci USA 104:20878–20883PubMedGoogle Scholar
  69. 69.
    Poggi M, Engel D, Christ A et al (2011) CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice. Arterioscler Thromb Vasc Biol 31:2251–2260PubMedGoogle Scholar
  70. 70.
    Wolf D, Jehle F, Ortiz Rodriguez A et al (2012) CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies. PLoS ONE 7:e33026PubMedCentralPubMedGoogle Scholar
  71. 71.
    Guo CA, Kogan S, Amano SU et al (2013) CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance. Am J Physiol Endocrinol Metab 304:E951–E963PubMedGoogle Scholar
  72. 72.
    Hamada M, Abe M, Miyake T et al (2011) B cell-activating factor controls the production of adipokines and induces insulin resistance. Obesity (Silver Spring) 19:1915–1922Google Scholar
  73. 73.
    Tada F, Abe M, Kawasaki K et al (2013) B cell activating factor in obesity is regulated by oxidative stress in adipocytes. J Clin Biochem Nutr 52:120–127PubMedCentralPubMedGoogle Scholar
  74. 74.
    Nikolajczyk BS, Jagannathan-Bogdan M, Shin H, Gyurko R (2011) State of the union between metabolism and the immune system in type 2 diabetes. Genes Immun 12:239–250PubMedGoogle Scholar
  75. 75.
    Mito N, Kaburagi T, Yoshino H, Imai A, Sato K (2006) Oral-tolerance induction in diet-induced obese mice. Life Sci 79:1056–1061PubMedGoogle Scholar
  76. 76.
    Palming J, Gabrielsson BG, Jennische E et al (2006) Plasma cells and Fc receptors in human adipose tissue–lipogenic and anti-inflammatory effects of immunoglobulins on adipocytes. Biochem Biophys Res Commun 343:43–48PubMedGoogle Scholar
  77. 77.
    Mamane Y, Chung Chan C, Lavallee G et al (2009) The C3a anaphylatoxin receptor is a key mediator of insulin resistance and functions by modulating adipose tissue macrophage infiltration and activation. Diabetes 58:2006–2017PubMedGoogle Scholar
  78. 78.
    Shulzhenko N, Morgun A, Hsiao W et al (2011) Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med 17:1585–1593PubMedCentralPubMedGoogle Scholar
  79. 79.
    Tilg H, Kaser A (2011) Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest 121:2126–2132PubMedCentralPubMedGoogle Scholar
  80. 80.
    Qin J, Li Y, Cai Z et al (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60PubMedGoogle Scholar
  81. 81.
    Lam YY, Ha CW, Campbell CR et al (2012) Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS ONE 7:e34233PubMedCentralPubMedGoogle Scholar
  82. 82.
    Wang Y, Li J, Tang L, Charnigo R, de Villiers W, Eckhardt E (2010) T-lymphocyte responses to intestinally absorbed antigens can contribute to adipose tissue inflammation and glucose intolerance during high-fat feeding. PLoS ONE 5:e13951PubMedCentralPubMedGoogle Scholar
  83. 83.
    Wang Y, Ghoshal S, Ward M, de Villiers W, Woodward J, Eckhardt E (2009) Chylomicrons promote intestinal absorption and systemic dissemination of dietary antigen (ovalbumin) in mice. PLoS ONE 4:e8442PubMedCentralPubMedGoogle Scholar
  84. 84.
    Ghoshal S, Witta J, Zhong J, de Villiers W, Eckhardt E (2009) Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res 50:90–97PubMedGoogle Scholar
  85. 85.
    Cani PD, Amar J, Iglesias MA et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772PubMedGoogle Scholar
  86. 86.
    Mohammed N, Tang L, Jahangiri A, de Villiers W, Eckhardt E (2012) Elevated IgG levels against specific bacterial antigens in obese patients with diabetes and in mice with diet-induced obesity and glucose intolerance. Metabolism 61:1211–1214PubMedCentralPubMedGoogle Scholar
  87. 87.
    Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917PubMedCentralPubMedGoogle Scholar
  88. 88.
    Alkhouri N, Gornicka A, Berk MP et al (2010) Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem 285:3428–3438PubMedGoogle Scholar
  89. 89.
    Wueest S, Rapold RA, Schumann DM et al (2010) Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice. J Clin Invest 120:191–202PubMedCentralPubMedGoogle Scholar
  90. 90.
    Gomez-Tourino I, Camina-Darriba F, Otero-Romero I et al (2010) Autoantibodies to glial fibrillary acid protein and S100beta in diabetic patients. Diabet Med 27:246–248PubMedGoogle Scholar
  91. 91.
    Yi CX, Tschop MH, Woods SC, Hofmann SM (2012) High-fat-diet exposure induces IgG accumulation in hypothalamic microglia. Dis Model Mech 5:686–690PubMedCentralPubMedGoogle Scholar
  92. 92.
    Winer S, Tsui H, Lau A et al (2003) Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive. Nat Med 9:198–205PubMedGoogle Scholar
  93. 93.
    Aran A, Weiner K, Lin L et al (2010) Post-streptococcal auto-antibodies inhibit protein disulfide isomerase and are associated with insulin resistance. PLoS ONE 5:e12875PubMedCentralPubMedGoogle Scholar
  94. 94.
    Chen R, Mias GI, Li-Pook-Than J et al (2012) Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 148:1293–1307PubMedCentralPubMedGoogle Scholar
  95. 95.
    Fredrikson GN, Anand DV, Hopkins D et al (2009) Associations between autoantibodies against apolipoprotein B-100 peptides and vascular complications in patients with type 2 diabetes. Diabetologia 52:1426–1433PubMedCentralPubMedGoogle Scholar
  96. 96.
    Zimering MB, Pan Z (2009) Autoantibodies in type 2 diabetes induce stress fiber formation and apoptosis in endothelial cells. J Clin Endocrinol Metab 94:2171–2177PubMedGoogle Scholar
  97. 97.
    Hempel P, Karczewski P, Kohnert KD et al (2009) Sera from patients with type 2 diabetes contain agonistic autoantibodies against G protein-coupled receptors. Scand J Immunol 70:159–160PubMedGoogle Scholar
  98. 98.
    Gabriel CL, Smith PB, Mendez-Fernandez YV, Wilhelm AJ, Ye AM, Major AS (2012) Autoimmune-mediated glucose intolerance in a mouse model of systemic lupus erythematosus. Am J Physiol Endocrinol Metab 303:E1313–E1324PubMedGoogle Scholar
  99. 99.
    Arai S, Maehara N, Iwamura Y et al (2013) Obesity-associated autoantibody production requires AIM to retain the immunoglobulin m immune complex on follicular dendritic cells. Cell Rep 3:1187–1198PubMedGoogle Scholar
  100. 100.
    Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR (1993) Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes 42:359–362PubMedGoogle Scholar
  101. 101.
    Larsen CM, Faulenbach M, Vaag A et al (2007) Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 356:1517–1526PubMedGoogle Scholar
  102. 102.
    Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE (2010) The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med 152:346–357PubMedCentralPubMedGoogle Scholar
  103. 103.
    Tesfa D, Ajeganova S, Hagglund H et al (2011) Late-onset neutropenia following rituximab therapy in rheumatic diseases: association with B lymphocyte depletion and infections. Arthritis Rheum 63:2209–2214PubMedGoogle Scholar
  104. 104.
    Rauch M, Tussiwand R, Bosco N, Rolink AG (2009) Crucial role for BAFF–BAFF-R signaling in the survival and maintenance of mature B cells. PLoS ONE 4:e5456PubMedCentralPubMedGoogle Scholar
  105. 105.
    Kyaw T, Tay C, Hosseini H et al (2012) Depletion of B2 but not B1a B cells in BAFF receptor-deficient ApoE mice attenuates atherosclerosis by potently ameliorating arterial inflammation. PLoS ONE 7:e29371PubMedCentralPubMedGoogle Scholar
  106. 106.
    Sage AP, Tsiantoulas D, Baker L et al (2012) BAFF receptor deficiency reduces the development of atherosclerosis in mice: brief report. Arterioscler Thromb Vasc Biol 32:1573–1576PubMedGoogle Scholar
  107. 107.
    Kawasaki K, Abe M, Tada F et al (2013) Blockade of B-cell-activating factor signaling enhances hepatic steatosis induced by a high-fat diet and improves insulin sensitivity. Lab Invest 93:311–321PubMedGoogle Scholar
  108. 108.
    Mingrone G, Panunzi S, De Gaetano A et al (2012) Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 366:1577–1585PubMedGoogle Scholar
  109. 109.
    Zhang H, Wang Y, Zhang J, Potter BJ, Sowers JR, Zhang C (2011) Bariatric surgery reduces visceral adipose inflammation and improves endothelial function in type 2 diabetic mice. Arterioscler Thromb Vasc Biol 31:2063–2069PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Daniel A. Winer
    • 1
    • 2
  • Shawn Winer
    • 1
    • 2
  • Melissa H. Y. Chng
    • 3
  • Lei Shen
    • 3
  • Edgar G. Engleman
    • 3
    Email author
  1. 1.Department of Pathology, Toronto General HospitalUniversity Health Network, University of TorontoTorontoCanada
  2. 2.Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI)University Health Network, University of TorontoTorontoCanada
  3. 3.Department of PathologyStanford University School of MedicinePalo AltoUSA

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