Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance, and Insulin Resistance

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 36, Issue 4, 2016, Pages 682-691

  Harmon, Daniel B ^a   Srikakulapu, Prasad ^a,b   Kaplan, Jennifer L ^a   Oldham, Stephanie N ^a   McSkimming, Chantel ^a   Garmey, James C ^a   Perry, Heather M ^a,b   Kirby, Jennifer L ^b   Prohaska, Thomas A ^c   Gonen, Ayelet ^c   Hallowell, Peter ^b   Schirmer, Bruce ^b   Tsimikas, Sotirios ^c   Taylor, Angela M ^b   Witztum, Joseph L ^c   McNamara, Coleen A ^a,b  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

adipose tissue; B cells; cytokines; inflammation; obesity

Indexed keywords

HIGH DENSITY LIPOPROTEIN; IMMUNOGLOBULIN M ANTIBODY; MALONALDEHYDE; PROTEIN KINASE B; AUTACOID; BIOLOGICAL MARKER; CYTOKINE; GLUCOSE BLOOD LEVEL; HOMEODOMAIN PROTEIN; IDB3 PROTEIN, MOUSE; IMMUNOGLOBULIN MU CHAIN; INHIBITOR OF DIFFERENTIATION PROTEIN; INSULIN; RAG-1 PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN ANTIBODY COMPLEX; ARTICLE; B 1B B CELL; B LYMPHOCYTE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; ENZYME PHOSPHORYLATION; EPIDIDYMIS FAT; GENOTYPE; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE; HUMAN; HUMAN TISSUE; INFLAMMATION; INSULIN RESISTANCE; INTRAABDOMINAL FAT; LIPID DIET; LYMPHOCYTE FUNCTION; MACROPHAGE; MOUSE; NONHUMAN; OBESITY; OXIDATION; PRIORITY JOURNAL; ADOPTIVE TRANSFER; ANIMAL; BLOOD; C57BL MOUSE; CELL CULTURE; COMPLICATION; DISEASE MODEL; GENETICS; GLUCOSE BLOOD LEVEL; IMMUNOLOGY; KNOCKOUT MOUSE; MALE; METABOLISM; PHENOTYPE; TIME FACTOR; TISSUE CULTURE TECHNIQUE; TRANSPLANTATION;

ADOPTIVE TRANSFER; ANIMALS; B-LYMPHOCYTE SUBSETS; BIOMARKERS; BLOOD GLUCOSE; CELLS, CULTURED; CYTOKINES; DISEASE MODELS, ANIMAL; GENOTYPE; GLUCOSE INTOLERANCE; HOMEODOMAIN PROTEINS; HUMANS; IMMUNOGLOBULIN MU-CHAINS; INFLAMMATION; INFLAMMATION MEDIATORS; INHIBITOR OF DIFFERENTIATION PROTEINS; INSULIN; INSULIN RESISTANCE; INTRA-ABDOMINAL FAT; MALE; MICE, INBRED C57BL; MICE, KNOCKOUT; OBESITY; PHENOTYPE; TIME FACTORS; TISSUE CULTURE TECHNIQUES;

EID: 84957927267     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.116.307166     Document Type: Article

References (58)

1. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18:363-374. doi: 10.1038/nm.2627.
2. Chawla A, Nguyen KD, Goh YP. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol. 2011;11:738-749. doi: 10.1038/ nri3071.
3. Chatzigeorgiou A, Karalis KP, Bornstein SR, Chavakis T. Lymphocytes in obesity-related adipose tissue inflammation. Diabetologia. 2012;55:2583-2592. doi: 10.1007/s00125-012-2607-0.
4. Winer DA, Winer S, Shen L, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17:610-617. doi: 10.1038/nm.2353.
5. Rangel-Moreno J, Moyron-Quiroz JE, Carragher DM, Kusser K, Hartson L, Moquin A, Randall TD. Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens. Immunity. 2009;30:731-743. doi: 10.1016/j. immuni.2009.03.014.
6. Duffaut C, Galitzky J, Lafontan M, Bouloumié A. Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun. 2009;384:482-485. doi: 10.1016/j. bbrc.2009.05.002.
7. Palming J, Gabrielsson BG, Jennische E, Smith U, Carlsson B, Carlsson LM, Lönn M. Plasma cells and Fc receptors in human adipose tissue- lipogenic and anti-inflammatory effects of immunoglobulins on adipocytes. Biochem Biophys Res Commun. 2006;343:43-48. doi: 10.1016/j. bbrc.2006.02.114.
8. Krist LF, Eestermans IL, Steenbergen JJ, Hoefsmit EC, Cuesta MA, Meyer S, Beelen RH. Cellular composition of milky spots in the human greater omentum: an immunochemical and ultrastructural study. Anat Rec. 1995;241:163-174. doi: 10.1002/ar.1092410204.
9. McDonnell ME, Ganley-Leal LM, Mehta A, Bigornia SJ, Mott M, Rehman Q, Farb MG, Hess DT, Joseph L, Gokce N, Apovian CM. B lymphocytes in human subcutaneous adipose crown-like structures. Obesity (Silver Spring). 2012;20:1372-1378. doi: 10.1038/oby.2012.54.
10. Rajewsky K. Clonal selection and learning in the antibody system. Nature. 1996;381:751-758. doi: 10.1038/381751a0.
11. Baumgarth N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat Rev Immunol. 2011;11:34-46. doi: 10.1038/ nri2901.
12. Thurnheer MC, Zuercher AW, Cebra JJ, Bos NA. B1 cells contribute to serum IgM, but not to intestinal IgA, production in gnotobiotic Ig allotype chimeric mice. J Immunol. 2003;170:4564-4571.
13. Stoehr AD, Schoen CT, Mertes MM, Eiglmeier S, Holecska V, Lorenz AK, Schommartz T, Schoen AL, Hess C, Winkler A, Wardemann H, Ehlers M. TLR9 in peritoneal B-1b cells is essential for production of protective self-reactive IgM to control Th17 cells and severe autoimmunity. J Immunol. 2011;187:2953-2965. doi: 10.4049/jimmunol.1003340.
14. Choi YS, Baumgarth N. Dual role for B-1a cells in immunity to influenza virus infection. J Exp Med. 2008;205:3053-3064. doi: 10.1084/ jem.20080979.
15. Alugupalli KR, Leong JM, Woodland RT, Muramatsu M, Honjo T, Gerstein RM. B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity. 2004;21:379-390. doi: 10.1016/j.immuni.2004.06.019.
16. Haas KM, Poe JC, Steeber DA, Tedder TF. B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. Immunity. 2005;23:7-18. doi: 10.1016/j.immuni.2005.04.011.
17. Binder CJ. Natural IgM antibodies against oxidation-specific epitopes. J Clin Immunol. 2010;30(suppl 1):S56-S60. doi: 10.1007/ s10875-010-9396-3.
18. Baumgarth N, Tung JW, Herzenberg LA. Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion. Springer Semin Immunopathol. 2005;26:347-362. doi: 10.1007/ s00281-004-0182-2.
19. Chen Y, Khanna S, Goodyear CS, Park YB, Raz E, Thiel S, Grönwall C, Vas J, Boyle DL, Corr M, Kono DH, Silverman GJ. Regulation of dendritic cells and macrophages by an anti-apoptotic cell natural antibody that suppresses TLR responses and inhibits inflammatory arthritis. J Immunol. 2009;183:1346-1359. doi: 10.4049/jimmunol.0900948.
20. Binder CJ, Hörkkö S, Dewan A, Chang MK, Kieu EP, Goodyear CS, Shaw PX, Palinski W, Witztum JL, Silverman GJ. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med. 2003;9:736-743. doi: 10.1038/nm876.
21. Hörkkö S, Bird DA, Miller E, Itabe H, Leitinger N, Subbanagounder G, Berliner JA, Friedman P, Dennis EA, Curtiss LK, Palinski W, Witztum JL. Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J Clin Invest. 1999;103:117-128. doi: 10.1172/ JCI4533.
22. Chou MY, Fogelstrand L, Hartvigsen K, Hansen LF, Woelkers D, Shaw PX, Choi J, Perkmann T, Bäckhed F, Miller YI, Hörkkö S, Corr M, Witztum JL, Binder CJ. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J Clin Invest. 2009;119:1335-1349. doi: 10.1172/JCI36800.
23. Mouthon L, Nobrega A, Nicolas N, Kaveri SV, Barreau C, Coutinho A, Kazatchkine MD. Invariance and restriction toward a limited set of self-antigens characterize neonatal IgM antibody repertoires and prevail in autoreactive repertoires of healthy adults. Proc Natl Acad Sci U S A. 1995;92:3839-3843.
24. Griffin DO, Holodick NE, Rothstein TL. Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+ CD27+ CD43+ CD70-. J Exp Med. 2011;208:67-80. doi: 10.1084/jem.20101499.
25. Pan L, Sato S, Frederick JP, Sun XH, Zhuang Y. Impaired immune responses and B-cell proliferation in mice lacking the Id3 gene. Mol Cell Biol. 1999;19:5969-5980.
26. Sugai M, Gonda H, Nambu Y, Yokota Y, Shimizu A. Role of Id proteins in B lymphocyte activation: new insights from knockout mouse studies. J Mol Med (Berl). 2004;82:592-599. doi: 10.1007/s00109-004-0562-z.
27. Hayakawa I, Tedder TF, Zhuang Y. B-lymphocyte depletion ameliorates Sjögren's syndrome in Id3 knockout mice. Immunology. 2007;122:73-79. doi: 10.1111/j.1365-2567.2007.02614.x.
28. Doran AC, Lipinski MJ, Oldham SN, et al. B-cell aortic homing and atheroprotection depend on Id3. Circ Res. 2012;110:e1-12. doi: 10.1161/ CIRCRESAHA.111.256438.
29. Lipinski MJ, Campbell KA, Duong SQ, Welch TJ, Garmey JC, Doran AC, Skaflen MD, Oldham SN, Kelly KA, McNamara CA. Loss of Id3 increases VCAM-1 expression, macrophage accumulation, and atherogenesis in Ldlr-/- mice. Arterioscler Thromb Vasc Biol. 2012;32:2855-2861. doi: 10.1161/ATVBAHA.112.300352.
30. Cutchins A, Harmon DB, Kirby JL, Doran AC, Oldham SN, Skaflen M, Klibanov AL, Meller N, Keller SR, Garmey J, McNamara CA. Inhibitor of differentiation-3 mediates high fat diet-induced visceral fat expansion. Arterioscler Thromb Vasc Biol. 2012;32:317-324. doi: 10.1161/ ATVBAHA.111.234856.
31. Perry HM, Oldham SN, Fahl SP, Que X, Gonen A, Harmon DB, Tsimikas S, Witztum JL, Bender TP, McNamara CA. Helix-loop-helix factor inhibitor of differentiation 3 regulates interleukin-5 expression and B-1a B cell proliferation. Arterioscler Thromb Vasc Biol. 2013;33:2771-2779. doi: 10.1161/ATVBAHA.113.302571.
32. Rosenfeld SM, Perry HM, Gonen A, Prohaska TA, Srikakulapu P, Grewal S, Das D, McSkimming C, Taylor AM, Tsimikas S, Bender TP, Witztum JL, McNamara CA. B-1b cells secrete atheroprotective IgM and attenuate atherosclerosis. Circ Res. 2015;117:e28-e39. doi: 10.1161/ CIRCRESAHA.117.306044.
33. Kitamura D, Roes J, Kühn R, Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991;350:423-426. doi: 10.1038/350423a0.
34. Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y, Tsuneyama K, Nagai Y, Takatsu K, Urakaze M, Kobayashi M, Tobe K. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes. 2009;58:2574-2582. doi: 10.2337/db08-1475.
35. Claflin JL, Cubberley M. Clonal nature of the immune response to phosphocholine. VII. Evidence throughout inbred mice for molecular similarities among antibodies bearing the T15 idiotype. J Immunol. 1980;125:551-558.
36. Shaw PX, Hörkkö S, Chang MK, Curtiss LK, Palinski W, Silverman GJ, Witztum JL. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J Clin Invest. 2000;105:1731-1740. doi: 10.1172/JCI8472.
37. Tsimikas S, Witztum JL, Miller ER, Sasiela WJ, Szarek M, Olsson AG, Schwartz GG; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial. Circulation. 2004;110:1406-1412. doi: 10.1161/01.CIR.0000141728.23033.B5.
38. Tsimikas S, Willeit P, Willeit J, Santer P, Mayr M, Xu Q, Mayr A, Witztum JL, Kiechl S. Oxidation-specific biomarkers, prospective 15-year cardiovascular and stroke outcomes, and net reclassification of cardiovascular events. J Am Coll Cardiol. 2012;60:2218-2229. doi: 10.1016/j.jacc.2012.08.979.
39. Murano I, Barbatelli G, Parisani V, Latini C, Muzzonigro G, Castellucci M, Cinti S. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res. 2008;49:1562-1568. doi: 10.1194/jlr.M800019-JLR200.
40. Wilkosz S, Ireland G, Khwaja N, Walker M, Butt R, de Giorgio-Miller A, Herrick SE. A comparative study of the structure of human and murine greater omentum. Anat Embryol (Berl). 2005;209:251-261. doi: 10.1007/ s00429-004-0446-6.
41. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 2010;463:540-544. doi: 10.1038/nature08636.
42. Baumgarth N, Jager GC, Herman OC, Herzenberg LA. CD4+ T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools. Proc Natl Acad Sci U S A. 2000;97:4766-4771.
43. Genestier L, Taillardet M, Mondiere P, Gheit H, Bella C, Defrance T. TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses. J Immunol. 2007;178:7779-7786.
44. Boes M, Esau C, Fischer MB, Schmidt T, Carroll M, Chen J. Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM. J Immunol. 1998;160:4776-4787.
45. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006;116:1494-1505. doi: 10.1172/ JCI26498.
46. Goff DC Jr, D'Agostino RB Jr, Haffner SM, Otvos JD. Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study. Metabolism. 2005;54:264-270. doi: 10.1016/j.metabol.2004.09.002.
47. Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, Pugh K, Jenkins AJ, Klein RL, Liao Y. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes. 2003;52:453-462.
48. DeFuria J, Belkina AC, Jagannathan-Bogdan M, et al. 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 U S A. 2013;110:5133-5138. doi: 10.1073/pnas.1215840110.
49. Jagannathan M, McDonnell M, Liang Y, Hasturk H, Hetzel J, Rubin D, Kantarci A, Van Dyke TE, Ganley-Leal LM, Nikolajczyk BS. Toll-like receptors regulate B cell cytokine production in patients with diabetes. Diabetologia. 2010;53:1461-1471. doi: 10.1007/s00125-010-1730-z.
50. Shen L, Chng MH, Alonso MN, Yuan R, Winer DA, Engleman EG. B- 1a lymphocytes attenuate insulin resistance. Diabetes. 2015;64:593-603. doi: 10.2337/db14-0554.
51. Nishimura S, Manabe I, Takaki S, Nagasaki M, Otsu M, Yamashita H, Sugita J, Yoshimura K, Eto K, Komuro I, Kadowaki T, Nagai R. Adipose natural regulatory B cells negatively control adipose tissue inflammation. Cell Metab. 2013;18:759-766
52. Wu L, Parekh VV, Hsiao J, Kitamura D, Van Kaer L. Spleen supports a pool of innate-like B cells in white adipose tissue that protects against obesity-associated insulin resistance. Proc Natl Acad Sci U S A. 2014;111:E4638-E4647. doi: 10.1073/pnas.1324052111.
53. Ghosn EE, Yamamoto R, Hamanaka S, Yang Y, Herzenberg LA, Nakauchi H, Herzenberg LA. Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells. Proc Natl Acad Sci U S A. 2012;109:5394-5398. doi: 10.1073/pnas.1121632109.
54. Rask-Madsen C, Kahn CR. Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2012;32:2052-2059. doi: 10.1161/ATVBAHA.111.241919.
55. Chang MK, Binder CJ, Miller YI, Subbanagounder G, Silverman GJ, Berliner JA, Witztum JL. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med. 2004;200:1359-1370. doi: 10.1084/jem.20031763.
56. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347-2355. doi: 10.1194/jlr.M500294-JLR200.
57. Bird DA, Gillotte KL, Hörkkö S, Friedman P, Dennis EA, Witztum JL, Steinberg D. Receptors for oxidized low-density lipoprotein on elicited mouse peritoneal macrophages can recognize both the modified lipid moieties and the modified protein moieties: implications with respect to macrophage recognition of apoptotic cells. Proc Natl Acad Sci U S A. 1999;96:6347-6352.
58. Rao F, Schork AJ, Maihofer AX, Nievergelt CM, Marcovina SM, Miller ER, Witztum JL, O'Connor DT, Tsimikas S. Heritability of biomarkers of oxidized lipoproteins: twin pair study. Arterioscler Thromb Vasc Biol. 2015;35:1704-1711. doi: 10.1161/ATVBAHA.115.305306.