Defects in germinal center selection in SLE

Frontiers in Immunology

Volumn 6, Issue AUG, 2015, Pages

  Woods, Megan ^a   Zou, Yong Rui ^a   Davidson, Anne ^a  

^a FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH   (United States)

Author keywords

Autoimmunity; B cell; Germinal center; SLE; Tolerance mechanisms

Indexed keywords

ABATACEPT; AUTOANTIBODY; AUTOANTIGEN; B CELL ACTIVATING FACTOR; B LYMPHOCYTE RECEPTOR; CD150 ANTIGEN; CD40 LIGAND; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR4; CHEMOKINE RECEPTOR CXCR5; GAMMA INTERFERON; IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN M ANTIBODY; NUCLEIC ACID; P SELECTIN GLYCOPROTEIN LIGAND 1; TOLL LIKE RECEPTOR 7;

APOPTOSIS; AUTOIMMUNITY; B LYMPHOCYTE; CELL DEATH; CELL EXPANSION; CELL MATURATION; CELL MIGRATION; CELL SELECTION; DNA POLYMORPHISM; GERMINAL CENTER; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; INTERNALIZATION; NONHUMAN; PROTEIN EXPRESSION; SHORT SURVEY; SOMATIC MUTATION; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE;

EID: 84941278040     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00425     Document Type: Short Survey

References (91)

1. Kerfoot SM, Yaari G, Patel JR, Johnson KL, Gonzalez DG, Kleinstein SH, et al. Germinal center B cell and T follicular helper cell development initiates in the interfollicular zone. Immunity (2011) 34(6):947-60. doi: 10.1016/j.immuni.2011.03.024.
2. Choi YS, Kageyama R, Eto D, Escobar TC, Johnston RJ, Monticelli L, et al. ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity (2011) 34(6):932-46. doi:10.1016/j.immuni.2011.03.023.
3. Liu D, Xu H, Shih C, Wan Z, Ma X, Ma W, et al. T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction. Nature (2015) 517(7533):214-8. doi:10.1038/nature13803.
4. Dal Porto JM, Haberman AM, Shlomchik MJ, Kelsoe G. Antigen drives very low affinity B cells to become plasmacytes and enter germinal centers. J Immunol (1998) 161(10):5373-81.
5. Nurieva RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L, et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity (2008) 29(1):138-49. doi:10.1016/j.immuni.2008.05.009.
6. Gatto D, Paus D, Basten A, Mackay CR, Brink R. Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses. Immunity (2009) 31(2):259-69. doi:10.1016/j.immuni.2009.06.016.
7. Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, et al. Oxysterols direct immune cell migration via EBI2. Nature (2011) 475(7357):524-7. doi:10.1038/nature10280.
8. Liu C, Yang XV, Wu J, Kuei C, Mani NS, Zhang L, et al. Oxysterols direct B-cell migration through EBI2. Nature (2011) 475(7357):519-23. doi:10.1038/nature10226.
9. Pereira JP, Kelly LM, Xu Y, Cyster JG. EBI2 mediates B cell segregation between the outer and centre follicle. Nature (2009) 460(7259):1122-6. doi:10.1038/nature08226.
10. Victora GD, Nussenzweig MC. Germinal centers. Annu Rev Immunol (2012) 30:429-57. doi:10.1146/annurev-immunol-020711-075032.
11. De Silva NS, Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol (2015) 15(3):137-48. doi:10.1038/nri3804.
12. Jarjour M, Jorquera A, Mondor I, Wienert S, Narang P, Coles MC, et al. Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells. J Exp Med (2014) 211(6):1109-22. doi:10.1084/jem.20132409.
13. El Shikh ME, El Sayed RM, Sukumar S, Szakal AK, Tew JG. Activation of B cells by antigens on follicular dendritic cells. Trends Immunol (2010) 31(6):205-11. doi:10.1016/j.it.2010.03.002.
14. Heesters BA, Myers RC, Carroll MC. Follicular dendritic cells: dynamic antigen libraries. Nat Rev Immunol (2014) 14(7):495-504. doi:10.1038/nri3689.
15. Aguzzi A, Kranich J, Krautler NJ. Follicular dendritic cells: origin, phenotype, and function in health and disease. Trends Immunol (2014) 35(3):105-13. doi:10.1016/j.it.2013.11.001.
16. Allen CD, Ansel KM, Low C, Lesley R, Tamamura H, Fujii N, et al. Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat Immunol (2004) 5(9):943-52. doi:10.1038/ni1100.
17. Allen CD, Okada T, Tang HL, Cyster JG. Imaging of germinal center selection events during affinity maturation. Science (2007) 315(5811):528-31. doi:10.1126/science.1136736.
18. Hauser AE, Junt T, Mempel TR, Sneddon MW, Kleinstein SH, Henrickson SE, et al. Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns. Immunity (2007) 26(5):655-67. doi:10.1016/j.immuni.2007.04.008.
19. Schwickert TA, Lindquist RL, Shakhar G, Livshits G, Skokos D, Kosco-Vilbois MH, et al. In vivo imaging of germinal centres reveals a dynamic open structure. Nature (2007) 446(7131):83-7. doi:10.1038/nature05573.
20. Bannard O, Horton RM, Allen CD, An J, Nagasawa T, Cyster JG. Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection. Immunity (2013) 39(5):912-24. doi:10.1016/j.immuni.2013.08.038.
21. Gitlin AD, Shulman Z, Nussenzweig MC. Clonal selection in the germinal centre by regulated proliferation and hypermutation. Nature (2014) 509(7502):637-40. doi:10.1038/nature13300.
22. Wang X, Cho B, Suzuki K, Xu Y, Green JA, An J, et al. Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers. J Exp Med (2011) 208(12):2497-510. doi:10.1084/jem.20111449.
23. Cannons JL, Lu KT, Schwartzberg PL. T follicular helper cell diversity and plasticity. Trends Immunol (2013) 34(5):200-7. doi:10.1016/j.it.2013.01.001.
24. Craft JE. Follicular helper T cells in immunity and systemic autoimmunity. Nat Rev Rheumatol (2012) 8(6):337-47. doi:10.1038/nrrheum.2012.58.
25. Ueno H, Banchereau J, Vinuesa CG. Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol (2015) 16(2):142-52. doi:10.1038/ni.3054.
26. Sage PT, Sharpe AH. T follicular regulatory cells in the regulation of B cell responses. Trends Immunol (2015) 36(7):410-8. doi:10.1016/j.it.2015.05.005.
27. Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol (2010) 11(1):7-13. doi:10.1038/ni.1818.
28. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science (2008) 322(5899):271-5. doi:10.1126/science.1160062.
29. Kim HJ, Cantor H. Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells. Semin Immunol (2011) 23(6):446-52. doi:10.1016/j.smim.2011.06.001.
30. Goodnow CC. Multistep pathogenesis of autoimmune disease. Cell (2007) 130(1):25-35. doi:10.1016/j.cell.2007.06.033.
31. Goodnow CC, Vinuesa CG, Randall KL, Mackay F, Brink R. Control systems and decision making for antibody production. Nat Immunol (2010) 11(8):681-8. doi:10.1038/ni.1900.
32. Brink R. The imperfect control of self-reactive germinal center B cells. Curr Opin Immunol (2014) 28:97-101. doi:10.1016/j.coi.2014.03.001.
33. Manson JJ, Mauri C, Ehrenstein MR. Natural serum IgM maintains immunological homeostasis and prevents autoimmunity. Springer Semin Immunopathol (2005) 26(4):425-32. doi:10.1007/s00281-004-0187-x.
34. Yachimovich-Cohen N, Fischel R, Bachar N, Yarkoni Y, Eilat D. Autoimmune NZB/NZW F1 mice utilize B cell receptor editing for generating high-affinity anti-dsDNA autoantibodies from low-affinity precursors. Eur J Immunol (2003) 33(9):2469-78. doi:10.1002/eji.200324025.
35. Yachimovich N, Mostoslavsky G, Yarkoni Y, Verbovetski I. The efficiency of B cell receptor (BCR) editing is dependent on BCR light chain rearrangement status. Eur J Immunol (2002) 32(4):1164-74. doi:10.1002/1521-4141(200204)32.
36. Friedmann D, Yachimovich N, Mostoslavsky G, Pewzner-Jung Y, Ben-Yehuda A, Rajewsky K, et al. Production of high affinity autoantibodies in autoimmune New Zealand Black/New Zealand white F1 mice targeted with an anti-DNA heavy chain. J Immunol (1999) 162(8):4406-16.
37. Pewzner-Jung Y, Friedmann D, Sonoda E, Jung S, Rajewsky K, Eilat D. B cell deletion, anergy, and receptor editing in "knock in" mice targeted with a germline-encoded or somatically mutated anti-DNA heavy chain. J Immunol (1998) 161(9):4634-45.
38. Huang W, Moisini I, Bethunaickan R, Sahu R, Akerman M, Eilat D, et al. BAFF/APRIL inhibition decreases selection of naive but not antigen-induced autoreactive B cells in murine systemic lupus erythematosus. J Immunol (2011) 187(12):6571-80. doi:10.4049/jimmunol.1101784.
39. Radic MZ, Mascelli MA, Erikson J, Shan H, Weigert M. Ig H and L chain contributions to autoimmune specificities. J Immunol (1991) 146(1):176-82.
40. Radic MZ, Erikson J, Litwin S, Weigert M. B lymphocytes may escape tolerance by revising their antigen receptors. J Exp Med (1993) 177(4):1165-73. doi:10.1084/jem.177.4.1165.
41. Paul E, Lutz J, Erikson J, Carroll MC. Germinal center checkpoints in B cell tolerance in 3H9 transgenic mice. Int Immunol (2004) 16(2):377-84. doi:10.1093/intimm/dxh035.
42. Li Y, Li H, Ni D, Weigert M. Anti-DNA B cells in MRL/lpr mice show altered differentiation and editing pattern. J Exp Med (2002) 196(12):1543-52. doi:10.1084/jem.20021560.
43. Moisini I, Huang W, Bethunaickan R, Sahu R, Ricketts PG, Akerman M, et al. The Yaa locus and IFN-alpha fine-tune germinal center B cell selection in murine systemic lupus erythematosus. J Immunol (2012) 189(9):4305-12. doi:10.4049/jimmunol.1200745.
44. Yurasov S, Wardemann H, Hammersen J, Tsuiji M, Meffre E, Pascual V, et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J Exp Med (2005) 201(5):703-11. doi:10.1084/jem.20042251.
45. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science (2003) 301(5638):1374-7. doi:10.1126/science.1086907.
46. Scheid JF, Mouquet H, Kofer J, Yurasov S, Nussenzweig MC, Wardemann H. Differential regulation of self-reactivity discriminates between IgG+ human circulating memory B cells and bone marrow plasma cells. Proc Natl Acad Sci U S A (2011) 108(44):18044-8. doi:10.1073/pnas.1113395108.
47. Tiller T, Tsuiji M, Yurasov S, Velinzon K, Nussenzweig MC, Wardemann H. Autoreactivity in human IgG+ memory B cells. Immunity (2007) 26(2):205-13. doi:10.1016/j.immuni.2007.01.009.
48. Cappione A III, Anolik JH, Pugh-Bernard A, Barnard J, Dutcher P, Silverman G, et al. Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. J Clin Invest (2005) 115(11):3205-16. doi:10.1172/JCI24179.
49. Mietzner B, Tsuiji M, Scheid J, Velinzon K, Tiller T, Abraham K, et al. Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors. Proc Natl Acad Sci U S A (2008) 105(28):9727-32. doi:10.1073/pnas.0803644105.
50. Mohan C, Alas E, Morel L, Yang P, Wakeland EK. Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes. J Clin Invest (1998) 101(6):1362-72.
51. Vuyyuru R, Mohan C, Manser T, Rahman ZS. The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints. J Immunol (2009) 183(9):5716-27. doi:10.4049/jimmunol.0804215.
52. Wong EB, Soni C, Chan AY, Domeier PP, Abraham T, Limaye N, et al. B cell-intrinsic CD84 and Ly108 maintain germinal center B cell tolerance. J Immunol (2015) 194(9):4130-43. doi:10.4049/jimmunol.1403023.
53. Sinai P, Dozmorov IM, Song R, Schwartzberg PL, Wakeland EK, Wulfing C. T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice. Eur J Immunol (2014) 44(12):3522-31. doi:10.1002/eji.201444602.
54. Rahman ZS, Manser T. Failed up-regulation of the inhibitory IgG Fc receptor Fc gamma RIIB on germinal center B cells in autoimmune-prone mice is not associated with deletion polymorphisms in the promoter region of the Fc gamma RIIB gene. J Immunol (2005) 175(3):1440-9. doi:10.4049/jimmunol.175.3.1440.
55. Mackay M, Stanevsky A, Wang T, Aranow C, Li M, Koenig S, et al. Selective dysregulation of the FcgammaIIB receptor on memory B cells in SLE. J Exp Med (2006) 203(9):2157-64. doi:10.1084/jem.20051503.
56. Pritchard NR, Cutler AJ, Uribe S, Chadban SJ, Morley BJ, Smith KG. Autoimmune-prone mice share a promoter haplotype associated with reduced expression and function of the Fc receptor FcgammaRII. Curr Biol (2000) 10(4):227-30. doi:10.1016/S0960-9822(00)00344-4.
57. Fukuyama H, Nimmerjahn F, Ravetch JV. The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells. Nat Immunol (2005) 6(1):99-106. doi:10.1038/ni1151.
58. Vogel KU, Edelmann SL, Jeltsch KM, Bertossi A, Heger K, Heinz GA, et al. Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation. Immunity (2013) 38(4):655-68. doi:10.1016/j.immuni.2012.12.004.
59. Linterman MA, Rigby RJ, Wong R, Silva D, Withers D, Anderson G, et al. Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS. Immunity (2009) 30(2):228-41. doi:10.1016/j.immuni.2008.12.015.
60. Jacquemin C, Schmitt N, Contin-Bordes C, Liu Y, Narayanan P, Seneschal J, et al. OX40 ligand contributes to human lupus pathogenesis by promoting T Follicular helper response. Immunity (2015) 42(6):1159-70. doi:10.1016/j.immuni.2015.05.012.
61. Liu Z, Bethunaickan R, Huang W, Lodhi U, Solano I, Madaio MP, et al. Interferon-alpha accelerates murine systemic lupus erythematosus in a T cell-dependent manner. Arthritis Rheum (2011) 63(1):219-29. doi:10.1002/art.30087.
62. Subramanian S, Tus K, Li QZ, Wang A, Tian XH, Zhou J, et al. A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc Natl Acad Sci U S A (2006) 103(26):9970-5. doi:10.1073/pnas.0603912103.
63. Christensen SR, Shupe J, Nickerson K, Kashgarian M, Flavell RA, Shlomchik MJ. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity (2006) 25(3):417-28. doi:10.1016/j.immuni.2006.07.013.
64. Jackson SW, Scharping NE, Kolhatkar NS, Khim S, Schwartz MA, Li QZ, et al. Opposing impact of B cell-intrinsic TLR7 and TLR9 signals on autoantibody repertoire and systemic inflammation. J Immunol (2014) 192(10):4525-32. doi:10.4049/jimmunol.1400098.
65. Christensen SR, Shlomchik MJ. Regulation of lupus-related autoantibody production and clinical disease by Toll-like receptors. Semin Immunol (2007) 19(1):11-23. doi:10.1016/j.smim.2006.12.005.
66. Clingan JM, Matloubian M. B Cell-intrinsic TLR7 signaling is required for optimal B cell responses during chronic viral infection. J Immunol (2013) 191(2):810-8. doi:10.4049/jimmunol.1300244.
67. Hwang SH, Lee H, Yamamoto M, Jones LA, Dayalan J, Hopkins R, et al. B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus-prone mice. J Immunol (2012) 189(12):5786-96. doi:10.4049/jimmunol.1202195.
68. Thibault DL, Chu AD, Graham KL, Balboni I, Lee LY, Kohlmoos C, et al. IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in mice. J Clin Invest (2008) 118(4):1417-26. doi:10.1172/JCI30065.
69. Boneparth A, Huang W, Bethunaickan R, Woods M, Sahu R, Arora S, et al. TLR7 influences germinal center selection in murine SLE. PLoS One (2015) 10(3):e0119925. doi:10.1371/journal.pone.0119925.
70. Mackay F, Schneider P. Cracking the BAFF code. Nat Rev Immunol (2009) 9(7):491-502. doi:10.1038/nri2572.
71. Goenka R, Scholz JL, Sindhava VJ, Cancro MP. New roles for the BLyS/BAFF family in antigen-experienced B cell niches. Cytokine Growth Factor Rev (2014) 25(2):107-13. doi:10.1016/j.cytogfr.2014.01.001.
72. Rahman ZS, Rao SP, Kalled SL, Manser T. Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice. J Exp Med (2003) 198(8):1157-69. doi:10.1084/jem.20030495.
73. Ou X, Xu S, Lam KP. Deficiency in TNFRSF13B (TACI) expands T-follicular helper and germinal center B cells via increased ICOS-ligand expression but impairs plasma cell survival. Proc Natl Acad Sci U S A (2012) 109(38):15401-6. doi:10.1073/pnas.1200386109.
74. Goenka R, Matthews AH, Zhang B, O'Neill PJ, Scholz JL, Migone TS, et al. Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation. J Exp Med (2014) 211(1):45-56. doi:10.1084/jem.20130505.
75. Scapini P, Hu Y, Chu CL, Migone TS, Defranco AL, Cassatella MA, et al. Myeloid cells, BAFF, and IFN-{gamma} establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice. J Exp Med (2010) 207(8):1757-73. doi:10.1084/jem.20100086.
76. Coquery CM, Loo WM, Wade NS, Bederman AG, Tung KS, Lewis JE, et al. BAFF regulates follicular helper t cells and affects their accumulation and interferon-gamma production in autoimmunity. Arthritis Rheumatol (2015) 67(3):773-84. doi:10.1002/art.38950.
77. Odegard JM, Marks BR, DiPlacido LD, Poholek AC, Kono DH, Dong C, et al. ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. J Exp Med (2008) 205(12):2873-86. doi:10.1084/jem.20080840.
78. Bubier JA, Sproule TJ, Foreman O, Spolski R, Shaffer DJ, Morse HC III, et al. A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice. Proc Natl Acad Sci U S A (2009) 106(5):1518-23. doi:10.1073/pnas.0807309106.
79. Ramanujam M, Kahn P, Huang W, Tao H, Madaio MP, Factor SM, et al. Interferon-alpha treatment of female (NZW x BXSB)F(1) mice mimics some but not all features associated with the Yaa mutation. Arthritis Rheum (2009) 60(4):1096-101. doi:10.1002/art.24414.
80. Groom JR, Fletcher CA, Walters SN, Grey ST, Watt SV, Sweet MJ, et al. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med (2007) 204(8):1959-71. doi:10.1084/jem.20062567.
81. Tipton CM, Fucile CF, Darce J, Chida A, Ichikawa T, Gregoretti I, et al. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat Immunol (2015) 16(7):755-65. doi:10.1038/ni.3175.
82. Takahashi Y, Ohta H, Takemori T. Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire. Immunity (2001) 14(2):181-92. doi:10.1016/S1074-7613(01)00100-5.
83. Ray SK, Putterman C, Diamond B. Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease. Proc Natl Acad Sci U S A (1996) 93(5):2019-24. doi:10.1073/pnas.93.5.2019.
84. Peperzak V, Vikstrom IB, Tarlinton DM. Through a glass less darkly: apoptosis and the germinal center response to antigen. Immunol Rev (2012) 247(1):93-106. doi:10.1111/j.1600-065X.2012.01123.x.
85. Rahman ZS. Impaired clearance of apoptotic cells in germinal centers: implications for loss of B cell tolerance and induction of autoimmunity. Immunol Res (2011) 51(2-3):125-33. doi:10.1007/s12026-011-8248-4.
86. Leffler J, Bengtsson AA, Blom AM. The complement system in systemic lupus erythematosus: an update. Ann Rheum Dis (2014) 73(9):1601-6. doi:10.1136/annrheumdis-2014-205287.
87. Hanayama R, Tanaka M, Miyasaka K, Aozasa K, Koike M, Uchiyama Y, et al. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science (2004) 304(5674):1147-50. doi:10.1126/science.109435.
88. Davidson A, Aranow C. Lupus nephritis: lessons from murine models. Nat Rev Rheumatol (2010) 6(1):13-20. doi:10.1038/nrrheum.2009.240.
89. Wang X, Huang W, Mihara M, Sinha J, Davidson A. Mechanism of action of combined short-term CTLA4Ig and anti-CD40 ligand in murine systemic lupus erythematosus. J Immunol (2002) 168(4):2046-53. doi:10.4049/jimmunol.168.4.2046.
90. Foell J, Strahotin S, O'Neil SP, McCausland MM, Suwyn C, Haber M, et al. CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB x NZW F1 mice. J Clin Invest (2003) 111(10):1505-18. doi:10.1172/JCI200317662.
91. Kinloch AJ, Chang A, Ko K, Henry Dunand CJ, Henderson S, Maienschein-Cline M, et al. Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis. Arthritis Rheumatol (2014) 66(12):3359-70. doi:10.1002/art.38888.