Inflammation Research

, 58:345 | Cite as

Killer B lymphocytes: the evidence and the potential



Immune regulation plays a critical role in controlling potentially dangerous inflammation and maintaining health. The Fas ligand/Fas receptor axis has been studied extensively as a mechanism of killing T cells and other cells during infections, autoimmunity, and cancer. FasL expression has been primarily attributed to activated T cells and NK cells. Evidence has emerged that B lymphocytes can express FasL and other death-inducing ligands, and can mediate cell death under many circumstances. Among B cell subsets, the expression of both Fas ligand and IL-10 is highest on the CD5+ B cell population, suggesting that CD5+ B cells may have a specialized regulatory function. The relevance of killer B cells to normal immune regulation, disease pathogenesis, and inflammation is discussed.


B lymphocytes Immune regulation Fas ligand Th cell apoptosis Cell-based therapy 


  1. 1.
    Acosta Rodriguez EV, Zuniga E, Montes CL, Gruppi A. Interleukin-4 biases differentiation of B cells from Trypanosoma cruzi-infected mice and restrains their fratricide: role of Fas ligand down-regulation and MHC class II-transactivator up-regulation. J Leukoc Biol. 2003;73:127–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Ahuja A, Shupe J, Dunn R, Kashgarian M, Kehry MR, Shlomchik MJ. Depletion of B cells in murine lupus: efficacy and resistance. J Immunol. 2007;179:3351–61.PubMedGoogle Scholar
  3. 3.
    Akdis M, Trautmann A, Klunker S, Daigle I, Kucuksezer UC, Deglmann W, et al. T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells. FASEB J. 2003;17:1026–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Al-Qaoud KM, Fleischer B, Hoerauf A. The Xid defect imparts susceptibility to experimental murine filariosis—association with a lack of antibody and IL-10 production by B cells in response to phosphorylcholine. Int Immunol. 1998;10:17–25.PubMedCrossRefGoogle Scholar
  5. 5.
    Alderson MR, Lynch DH. Receptors and ligands that mediate activation-induced death of T cells. Springer Semin Immunopathol. 1998;19:289–300.PubMedCrossRefGoogle Scholar
  6. 6.
    Anel A, Bosque A, Naval J, Pineiro A, Larrad L, Alava MA, et al. Apo2L/TRAIL and immune regulation. Front Biosci. 2007;12:2074–84.PubMedCrossRefGoogle Scholar
  7. 7.
    Arnold LW, McCray SK, Tatu C, Clarke SH. Identification of a precursor to phosphatidyl choline-specific B-1 cells suggesting that B-1 cells differentiate from splenic conventional B cells in vivo: cyclosporin A blocks differentiation to B-1. J Immunol. 2000;164:2924–30.PubMedGoogle Scholar
  8. 8.
    Bonardelle D, Benihoud K, Kiger N, Bobe P. B lymphocytes mediate Fas-dependent cytotoxicity in MRL/lpr mice. J Leukoc Biol. 2005;78:1052–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Boros DL. Immunoregulation of granuloma formation in murine schistosomiasis mansoni. Ann N Y Acad Sci. 1986;465:313–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Boros DL. T helper cell populations, cytokine dynamics, and pathology of the schistosome egg granuloma. Microbes Infect. 1999;1:511–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Bussing A, Stein GM, Pfuller U, Schietzel M. Induction of Fas ligand (CD95L) by the toxic mistletoe lectins in human lymphocytes. Anticancer Res. 1999;19:1785–90.PubMedGoogle Scholar
  12. 12.
    Carter LL, Leach MW, Azoitei ML, Cui J, Pelker JW, Jussif J, et al. PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2007;182:124–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Cheever AW, Byram JE, Hieny S, von Lichtenberg F, Lunde MN, Sher A. Immunopathology of Schistosoma japonicum and S. mansoni infection in B cell depleted mice. Parasite Immunol. 1985;7:399–413.PubMedCrossRefGoogle Scholar
  14. 14.
    Collins M, Ling V, Carreno BM. The B7 family of immune-regulatory ligands. Genome Biol. 2005;6:223.PubMedCrossRefGoogle Scholar
  15. 15.
    Cong YZ, Rabin E, Wortis HH. Treatment of murine CD5 B cells with anti-Ig, but not LPS, induces surface CD5: two B-cell activation pathways. Int Immunol. 1991;3:467–76.PubMedCrossRefGoogle Scholar
  16. 16.
    Cooke A, Tonks P, Jones FM, O’Shea H, Hutchings P, Fulford AJ, et al. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 1999;21:169–76.PubMedCrossRefGoogle Scholar
  17. 17.
    Duan B, Morel L. Role of B-1a cells in autoimmunity. Autoimmun Rev. 2006;5:403–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Duddy M, Niino M, Adatia F, Hebert S, Freedman M, Atkins H, et al. Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol. 2007;178:6092–9.PubMedGoogle Scholar
  19. 19.
    Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350:2572–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban JF Jr, et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2003;284:G385–91.PubMedGoogle Scholar
  21. 21.
    Elliott DE, Summers RW, Weinstock JV. Helminths as governors of immune-mediated inflammation. Int J Parasitol. 2007;37:457–64.PubMedCrossRefGoogle Scholar
  22. 22.
    Elpek KG, Lacelle C, Singh NP, Yolcu ES, Shirwan H. CD4+ CD25+ T regulatory cells dominate multiple immune evasion mechanisms in early but not late phases of tumor development in a B cell lymphoma model. J Immunol. 2007;178:6840–8.PubMedGoogle Scholar
  23. 23.
    Fillatreau S, Gray D, Anderton SM. Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol. 2008;8:391–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002;3:944–50.PubMedCrossRefGoogle Scholar
  25. 25.
    Fischer GM, Solt LA, Hastings WD, Yang K, Gerstein RM, Nikolajczyk BS, et al. Splenic and peritoneal B-1 cells differ in terms of transcriptional and proliferative features that separate peritoneal B-1 from splenic B-2 cells. Cell Immunol. 2001;213:62–71.PubMedCrossRefGoogle Scholar
  26. 26.
    Gagro A, McCloskey N, Challa A, Holder M, Grafton G, Pound JD, et al. CD5-positive and CD5-negative human B cells converge to an indistinguishable population on signalling through B-cell receptors and CD40. Immunology. 2000;101:201–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Gaubert S, Viana da Costa A, Maurage CA, Lima EC, Fontaine J, Lafitte S, et al. X-linked immunodeficiency affects the outcome of Schistosoma mansoni infection in the murine model. Parasite Immunol. 1999;21:89–101.PubMedCrossRefGoogle Scholar
  28. 28.
    Gourley TS, Patel DR, Nickerson K, Hong SC, Chang CH. Aberrant expression of Fas ligand in mice deficient for the MHC class II transactivator. J Immunol. 2002;168:4414–9.PubMedGoogle Scholar
  29. 29.
    Grullich C, Richter M, Exner S, Finke J. Fas ligand is not constitutively expressed in low-grade B-cell lymphoma and B-lymphoblastoid cells. Eur J Haematol. 2003;71:184–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Hahne M, Renno T, Schroeter M, Irmler M, French L, Bornard T, et al. Activated B cells express functional Fas ligand. Eur J Immunol. 1996;26:721–4.PubMedCrossRefGoogle Scholar
  31. 31.
    Hamaguchi Y, Uchida J, Cain DW, Venturi GM, Poe JC, Haas KM, et al. The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice. J Immunol. 2005;174:4389–99.PubMedGoogle Scholar
  32. 32.
    Hayakawa K, Asano M, Shinton SA, Gui M, Allman D, Stewart CL, et al. Positive selection of natural autoreactive B cells. Science. 1999;285:113–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Hayakawa K, Asano M, Shinton SA, Gui M, Wen LJ, Dashoff J, et al. Positive selection of anti-thy-1 autoreactive B-1 cells and natural serum autoantibody production independent from bone marrow B cell development. J Exp Med. 2003;197:87–99.PubMedCrossRefGoogle Scholar
  34. 34.
    Hitoshi Y, Okada Y, Sonoda E, Tominaga A, Makino M, Suzuki K, et al. Delayed progression of a murine retrovirus-induced acquired immunodeficiency syndrome in X-linked immunodeficient mice. J Exp Med. 1993;177:621–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Ishida M, Iwai Y, Tanaka Y, Okazaki T, Freeman GJ, Minato N, et al. Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues. Immunol Lett. 2002;84:57–62.PubMedCrossRefGoogle Scholar
  36. 36.
    Kemp TJ, Moore JM, Griffith TS. Human B cells express functional TRAIL/Apo-2 ligand after CpG-containing oligodeoxynucleotide stimulation. J Immunol. 2004;173:892–9.PubMedGoogle Scholar
  37. 37.
    Kim SH, Kim S, Oligino TJ, Robbins PD. Effective treatment of established mouse collagen-induced arthritis by systemic administration of dendritic cells genetically modified to express FasL. Mol Ther. 2002;6:584–90.PubMedCrossRefGoogle Scholar
  38. 38.
    Kim YS, Park GB, Song HK, Hur I, Lee HK, Kang JS, et al. Cross-linking of CD54 on Burkitt lymphoma cell line Raji and Ramos induces FasL expression by reactive oxygen species and apoptosis of adjacent cells in Fas/FasL interaction. J Immunother. 2007;30:727–39.PubMedCrossRefGoogle Scholar
  39. 39.
    Kojima Y, Tsurumi H, Goto N, Shimizu M, Kasahara S, Yamada T, et al. Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcome. Eur J Haematol. 2006;76:465–72.PubMedCrossRefGoogle Scholar
  40. 40.
    Kondo E, Yoshino T, Nishiuchi R, Sakuma I, Nishizaki K, Kayagaki N, et al. Expression of Fas ligand mRNA in germinal centres of the human tonsil. J Pathol. 1997;183:75–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Kosiewicz MM, Krishnan A, Worthington MT, Matriano JA, Ross WG. B cells engineered to express Fas ligand suppress pre-sensitized antigen-specific T cell responses in vivo. Eur J Immunol. 2002;32:1679–87.PubMedCrossRefGoogle Scholar
  42. 42.
    La Flamme AC, Ruddenklau K, Backstrom BT. Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun. 2003;71:4996–5004.PubMedCrossRefGoogle Scholar
  43. 43.
    Lampropoulou V, Hoehlig K, Roch T, Neves P, Gomez EC, Sweenie CH, et al. TLR-activated B cells suppress T cell-mediated autoimmunity. J Immunol. 2008;180:4763–73.PubMedGoogle Scholar
  44. 44.
    Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:613–20.PubMedCrossRefGoogle Scholar
  45. 45.
    Lund FE, Garvy BA, Randall TD, Harris DP. Regulatory roles for cytokine-producing B cells in infection and autoimmune disease. Curr Dir Autoimmun. 2005;8:25–54.PubMedCrossRefGoogle Scholar
  46. 46.
    Lund FE, Hollifield M, Schuer K, Lines JL, Randall TD, Garvy BA. B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection. J Immunol. 2006;176:6147–54.PubMedGoogle Scholar
  47. 47.
    Lundy SK, Berlin AA, Martens TF, Lukacs NW. Deficiency of regulatory B cells increases allergic airway inflammation. Inflamm Res. 2005;54:514–21.PubMedCrossRefGoogle Scholar
  48. 48.
    Lundy SK, Boros DL. Fas ligand-expressing B-1a lymphocytes mediate CD4(+)-T-cell apoptosis during schistosomal infection: induction by interleukin 4 (IL-4) and IL-10. Infect Immun. 2002;70:812–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Lundy SK, Lerman SP, Boros DL. Soluble egg antigen-stimulated T helper lymphocyte apoptosis and evidence for cell death mediated by FasL(+) T and B cells during murine Schistosoma mansoni infection. Infect Immun. 2001;69:271–80.PubMedCrossRefGoogle Scholar
  50. 50.
    Maglione PJ, Xu J, Chan J. B cells moderate inflammatory progression and enhance bacterial containment upon pulmonary challenge with Mycobacterium tuberculosis. J Immunol. 2007;178:7222–34.PubMedGoogle Scholar
  51. 51.
    Mangan NE, Fallon RE, Smith P, van Rooijen N, McKenzie AN, Fallon PG. Helminth infection protects mice from anaphylaxis via IL-10-producing B cells. J Immunol. 2004;173:6346–56.PubMedGoogle Scholar
  52. 52.
    Mann MK, Maresz K, Shriver LP, Tan Y, Dittel BN. B cell regulation of CD4+ CD25+ T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis. J Immunol. 2007;178:3447–56.PubMedGoogle Scholar
  53. 53.
    Mariani SM, Krammer PH. Differential regulation of TRAIL and CD95 ligand in transformed cells of the T and B lymphocyte lineage. Eur J Immunol. 1998;28:973–82.PubMedCrossRefGoogle Scholar
  54. 54.
    Mariani SM, Krammer PH. Surface expression of TRAIL/Apo-2 ligand in activated mouse T and B cells. Eur J Immunol. 1998;28:1492–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Martin F, Kearney JF. B1 cells: similarities and differences with other B cell subsets. Curr Opin Immunol. 2001;13:195–201.PubMedCrossRefGoogle Scholar
  56. 56.
    Mauri C, Ehrenstein MR. The ‘short’ history of regulatory B cells. Trends Immunol. 2008;29:34–40.PubMedCrossRefGoogle Scholar
  57. 57.
    Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003;197:489–501.PubMedCrossRefGoogle Scholar
  58. 58.
    Meiler F, Zimmermann M, Blaser K, Akdis CA, Akdis M. T-cell subsets in the pathogenesis of human asthma. Curr Allergy Asthma Rep. 2006;6:91–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Melo ME, Qian J, El-Amine M, Agarwal RK, Soukhareva N, Kang Y, et al. Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases. J Immunol. 2002;168:4788–95.PubMedGoogle Scholar
  60. 60.
    Mercolino TJ, Arnold LW, Hawkins LA, Haughton G. Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes. J Exp Med. 1988;168:687–98.PubMedCrossRefGoogle Scholar
  61. 61.
    Minagawa R, Okano S, Tomita Y, Kishihara K, Yamada H, Nomoto K, et al. The critical role of Fas–Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen. Transplantation. 2004;78:799–806.PubMedCrossRefGoogle Scholar
  62. 62.
    Minoprio P, el Cheikh MC, Murphy E, Hontebeyrie-Joskowicz M, Coffman R, Coutinho A, et al. Xid-associated resistance to experimental Chagas’ disease is IFN-gamma dependent. J Immunol. 1993;151:4200–8.PubMedGoogle Scholar
  63. 63.
    Mizoguchi A, Bhan AK. A case for regulatory B cells. J Immunol. 2006;176:705–10.PubMedGoogle Scholar
  64. 64.
    Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002;16:219–30.PubMedCrossRefGoogle Scholar
  65. 65.
    Montecino-Rodriguez E, Leathers H, Dorshkind K. Identification of a B-1 B cell-specified progenitor. Nat Immunol. 2006;7:293–301.PubMedCrossRefGoogle Scholar
  66. 66.
    Mullauer L, Mosberger I, Chott A. Fas ligand expression in nodal non-Hodgkin’s lymphoma. Mod Pathol. 1998;11:369–75.PubMedGoogle Scholar
  67. 67.
    Nagafuchi H, Wakisaka S, Takeba Y, Takeno M, Sakane T, Suzuki N. Aberrant expression of Fas ligand on anti-DNA autoantibody secreting B lymphocytes in patients with systemic lupus erythematosus: “immune privilege”-like state of the autoreactive B cells. Clin Exp Rheumatol. 2002;20:625–31.PubMedGoogle Scholar
  68. 68.
    Nilsson N, Ingvarsson S, Borrebaeck CA. Immature B cells in bone marrow express Fas/FasL. Scand J Immunol. 2000;51:279–84.PubMedCrossRefGoogle Scholar
  69. 69.
    Noorchashm H, Reed AJ, Rostami SY, Mozaffari R, Zekavat G, Koeberlein B, et al. B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection. J Immunol. 2006;177:7715–22.PubMedGoogle Scholar
  70. 70.
    O’Garra A, Howard M. IL-10 production by CD5 B cells. Ann N Y Acad Sci. 1992;651:182–99.PubMedCrossRefGoogle Scholar
  71. 71.
    Palanivel V, Posey C, Horauf AM, Solbach W, Piessens WF, Harn DA. B-cell outgrowth and ligand-specific production of IL-10 correlate with Th2 dominance in certain parasitic diseases. Exp Parasitol. 1996;84:168–77.PubMedCrossRefGoogle Scholar
  72. 72.
    Pers JO, Daridon C, Bendaoud B, Devauchelle V, Berthou C, Saraux A, et al. B-cell depletion and repopulation in autoimmune diseases. Clin Rev Allergy Immunol. 2008;34:50–5.PubMedCrossRefGoogle Scholar
  73. 73.
    Rich RF, Cook WJ, Green WR. Spontaneous in vivo retrovirus-infected T and B cells, but not dendritic cells, mediate antigen-specific Fas ligand/Fas-dependent apoptosis of anti-retroviral CTL. Virology. 2006;346:287–300.PubMedCrossRefGoogle Scholar
  74. 74.
    Sampalo A, Navas G, Medina F, Segundo C, Camara C, Brieva JA. Chronic lymphocytic leukemia B cells inhibit spontaneous Ig production by autologous bone marrow cells: role of CD95-CD95L interaction. Blood. 2000;96:3168–74.PubMedGoogle Scholar
  75. 75.
    Samuelsson A, Sonnerborg A, Heuts N, Coster J, Chiodi F. Progressive B cell apoptosis and expression of Fas ligand during human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses. 1997;13:1031–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Sasaki H, Schmitt DA, Matsumoto K, Pollard RB, Suzuki F. Demonstrations of a B-cell population that regulates the immune response in spleens of mice infected with herpes simplex virus type I. Clin Immunol Immunopathol. 1993;66:169–75.PubMedCrossRefGoogle Scholar
  77. 77.
    Sasaki Y, Ami Y, Nakasone T, Shinohara K, Takahashi E, Ando S, et al. Induction of CD95 ligand expression on T lymphocytes and B lymphocytes and its contribution to apoptosis of CD95-up-regulated CD4+ T lymphocytes in macaques by infection with a pathogenic simian/human immunodeficiency virus. Clin Exp Immunol. 2000;122:381–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Satpute SR, Soukhareva N, Scott DW, Moudgil KD. Mycobacterial Hsp65-IgG-expressing tolerogenic B cells confer protection against adjuvant-induced arthritis in Lewis rats. Arthritis Rheum. 2007;56:1490–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Sedger LM, Glaccum MB, Schuh JC, Kanaly ST, Williamson E, Kayagaki N, et al. Characterization of the in vivo function of TNF-alpha-related apoptosis-inducing ligand, TRAIL/Apo2L, using TRAIL/Apo2L gene-deficient mice. Eur J Immunol. 2002;32:2246–54.PubMedCrossRefGoogle Scholar
  80. 80.
    Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M, et al. Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol. 2003;15:59–69.PubMedCrossRefGoogle Scholar
  81. 81.
    Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8:239–45.PubMedCrossRefGoogle Scholar
  82. 82.
    Silvestris F, Cafforio P, Tucci M, Grinello D, Dammacco F. Upregulation of osteoblast apoptosis by malignant plasma cells: a role in myeloma bone disease. Br J Haematol. 2003;122:39–52.PubMedCrossRefGoogle Scholar
  83. 83.
    Silvestris F, Tucci M, Cafforio P, Dammacco F. Fas-L up-regulation by highly malignant myeloma plasma cells: role in the pathogenesis of anemia and disease progression. Blood. 2001;97:1155–64.PubMedCrossRefGoogle Scholar
  84. 84.
    Singh A, Carson WF, Secor ER Jr, Guernsey LA, Flavell RA, Clark RB, et al. Regulatory role of B cells in a murine model of allergic airway disease. J Immunol. 2008;180:7318–26.PubMedGoogle Scholar
  85. 85.
    Song H, Park G, Kim YS, Hur I, Kim H, Ryu JW, et al. B7–H4 reverse signaling induces the apoptosis of EBV-transformed B cells through Fas ligand up-regulation. Cancer Lett. 2008;266:227–37.PubMedCrossRefGoogle Scholar
  86. 86.
    Spencer NF, Daynes RA. IL-12 directly stimulates expression of IL-10 by CD5+ B cells and IL-6 by both CD5+ and CD5 B cells: possible involvement in age-associated cytokine dysregulation. Int Immunol. 1997;9:745–54.PubMedCrossRefGoogle Scholar
  87. 87.
    Strater J, Mariani SM, Walczak H, Rucker FG, Leithauser F, Krammer PH, et al. CD95 ligand (CD95L) in normal human lymphoid tissues: a subset of plasma cells are prominent producers of CD95L. Am J Pathol. 1999;154:193–201.PubMedGoogle Scholar
  88. 88.
    Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, et al. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994;76:969–76.PubMedCrossRefGoogle Scholar
  89. 89.
    Tang Y, Kim WK, Holmes KL, Hugin AW, Kenny JJ, Chattopadhyay SK, et al. Contribution of B cell subsets to delayed development of MAIDS in Xid mice. Cell Immunol. 1995;165:1–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Tanner JE, Alfieri C. Epstein–Barr virus induces Fas (CD95) in T cells and Fas ligand in B cells leading to T-cell apoptosis. Blood. 1999;94:3439–47.PubMedGoogle Scholar
  91. 91.
    Tian J, Zekzer D, Hanssen L, Lu Y, Olcott A, Kaufman DL. Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice. J Immunol. 2001;167:1081–9.PubMedGoogle Scholar
  92. 92.
    Tinhofer I, Marschitz I, Kos M, Henn T, Egle A, Villunger A, et al. Differential sensitivity of CD4+ and CD8+ T lymphocytes to the killing efficacy of Fas (Apo-1/CD95) ligand + tumor cells in B chronic lymphocytic leukemia. Blood. 1998;91:4273–81.PubMedGoogle Scholar
  93. 93.
    Truman JP, Choqueux C, Tschopp J, Vedrenne J, Le Deist F, Charron D, et al. HLA class II-mediated death is induced via Fas/Fas ligand interactions in human splenic B lymphocytes. Blood. 1997;89:1996–2007.PubMedGoogle Scholar
  94. 94.
    Tsitoura DC, Yeung VP, DeKruyff RH, Umetsu DT. Critical role of B cells in the development of T cell tolerance to aeroallergens. Int Immunol. 2002;14:659–67.PubMedCrossRefGoogle Scholar
  95. 95.
    Tumang JR, Hastings WD, Bai C, Rothstein TL. Peritoneal and splenic B-1 cells are separable by phenotypic, functional, and transcriptomic characteristics. Eur J Immunol. 2004;34:2158–67.PubMedCrossRefGoogle Scholar
  96. 96.
    Velupillai P, Harn DA. Oligosaccharide-specific induction of interleukin 10 production by B220+ cells from schistosome-infected mice: a mechanism for regulation of CD4+ T-cell subsets. Proc Natl Acad Sci U S A. 1994;91:18–22.PubMedCrossRefGoogle Scholar
  97. 97.
    Villunger A, Egle A, Marschitz I, Kos M, Bock G, Ludwig H, et al. Constitutive expression of Fas (Apo-1/CD95) ligand on multiple myeloma cells: a potential mechanism of tumor-induced suppression of immune surveillance. Blood. 1997;90:12–20.PubMedGoogle Scholar
  98. 98.
    Watt V, Ronchese F, Ritchie D. Resting B cells suppress tumor immunity via an MHC class-II dependent mechanism. J Immunother. 2007;30:323–32.PubMedCrossRefGoogle Scholar
  99. 99.
    Wei B, Velazquez P, Turovskaya O, Spricher K, Aranda R, Kronenberg M, et al. Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets. Proc Natl Acad Sci U S A. 2005;102:2010–5.PubMedCrossRefGoogle Scholar
  100. 100.
    Weinstock JV, Summers RW, Elliott DE, Qadir K, Urban JF Jr, Thompson R. The possible link between de-worming and the emergence of immunological disease. J Lab Clin Med. 2002;139:334–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Werner-Klein M, Dresch C, Marconi P, Brocker T. Transcriptional targeting of B cells for induction of peripheral CD8 T cell tolerance. J Immunol. 2007;178:7738–46.PubMedGoogle Scholar
  102. 102.
    Xiu Y, Wong CP, Bouaziz JD, Hamaguchi Y, Wang Y, Pop SM, et al. B lymphocyte depletion by CD20 monoclonal antibody prevents diabetes in nonobese diabetic mice despite isotype-specific differences in Fc{gamma}R effector functions. J Immunol. 2008;180:2863–75.PubMedGoogle Scholar
  103. 103.
    Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008;28:639–50.PubMedCrossRefGoogle Scholar
  104. 104.
    Yanaba K, Hamaguchi Y, Venturi GM, Steeber DA, St Clair EW, Tedder TF. B cell depletion delays collagen-induced arthritis in mice: arthritis induction requires synergy between humoral and cell-mediated immunity. J Immunol. 2007;179:1369–80.PubMedGoogle Scholar
  105. 105.
    Zhan HG, Mountz JD, Fleck M, Zhou T, Hsu HC. Specific deletion of autoreactive T cells by adenovirus-transfected, Fas ligand-producing antigen-presenting cells. Immunol Res. 2002;26:235–46.PubMedCrossRefGoogle Scholar
  106. 106.
    Zhang HG, Liu D, Heike Y, Yang P, Wang Z, Wang X, et al. Induction of specific T-cell tolerance by adenovirus-transfected, Fas ligand-producing antigen presenting cells. Nat Biotechnol. 1998;16:1045–9.PubMedCrossRefGoogle Scholar
  107. 107.
    Zhang X, Deriaud E, Jiao X, Braun D, Leclerc C, Lo-Man R. Type I interferons protect neonates from acute inflammation through interleukin 10-producing B cells. J Exp Med. 2007;204:1107–18.PubMedCrossRefGoogle Scholar
  108. 108.
    Zhong X, Tumang JR, Gao W, Bai C, Rothstein TL. PD-L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for V(H)11/V(H)12 and phosphatidylcholine binding. Eur J Immunol. 2007;37:2405–10.PubMedCrossRefGoogle Scholar
  109. 109.
    Zimecki M, Whiteley PJ, Pierce CW, Kapp JA. Presentation of antigen by B cells subsets. I. Lyb-5+ and Lyb-5 B cells differ in ability to stimulate antigen specific T cells. Arch Immunol Ther Exp (Warsz). 1994;42:115–23.Google Scholar
  110. 110.
    Zoi-Toli O, Meijer CJ, Oudejans JJ, de Vries E, van Beek P, Willemze R. Expression of Fas and Fas ligand in cutaneous B-cell lymphomas. J Pathol. 1999;189:533–8.PubMedCrossRefGoogle Scholar
  111. 111.
    Zuniga E, Motran CC, Montes CL, Yagita H, Gruppi A. Trypanosoma cruzi infection selectively renders parasite-specific IgG+ B lymphocytes susceptible to Fas/Fas ligand-mediated fratricide. J Immunol. 2002;168:3965–73.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA

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