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Killer B lymphocytes: the evidence and the potential

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Abstract

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.

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References

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  5. Alderson MR, Lynch DH. Receptors and ligands that mediate activation-induced death of T cells. Springer Semin Immunopathol. 1998;19:289–300.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  9. Boros DL. Immunoregulation of granuloma formation in murine schistosomiasis mansoni. Ann N Y Acad Sci. 1986;465:313–23.

    Article  PubMed  CAS  Google Scholar 

  10. Boros DL. T helper cell populations, cytokine dynamics, and pathology of the schistosome egg granuloma. Microbes Infect. 1999;1:511–6.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  14. Collins M, Ling V, Carreno BM. The B7 family of immune-regulatory ligands. Genome Biol. 2005;6:223.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  17. Duan B, Morel L. Role of B-1a cells in autoimmunity. Autoimmun Rev. 2006;5:403–8.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  21. Elliott DE, Summers RW, Weinstock JV. Helminths as governors of immune-mediated inflammation. Int J Parasitol. 2007;37:457–64.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  47. Lundy SK, Berlin AA, Martens TF, Lukacs NW. Deficiency of regulatory B cells increases allergic airway inflammation. Inflamm Res. 2005;54:514–21.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  55. Martin F, Kearney JF. B1 cells: similarities and differences with other B cell subsets. Curr Opin Immunol. 2001;13:195–201.

    Article  PubMed  CAS  Google Scholar 

  56. Mauri C, Ehrenstein MR. The ‘short’ history of regulatory B cells. Trends Immunol. 2008;29:34–40.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  63. Mizoguchi A, Bhan AK. A case for regulatory B cells. J Immunol. 2006;176:705–10.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  65. Montecino-Rodriguez E, Leathers H, Dorshkind K. Identification of a B-1 B cell-specified progenitor. Nat Immunol. 2006;7:293–301.

    Article  PubMed  CAS  Google Scholar 

  66. Mullauer L, Mosberger I, Chott A. Fas ligand expression in nodal non-Hodgkin’s lymphoma. Mod Pathol. 1998;11:369–75.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  68. Nilsson N, Ingvarsson S, Borrebaeck CA. Immature B cells in bone marrow express Fas/FasL. Scand J Immunol. 2000;51:279–84.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  70. O’Garra A, Howard M. IL-10 production by CD5 B cells. Ann N Y Acad Sci. 1992;651:182–99.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

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Acknowledgments

Thank you to David A. Fox and Dov L. Boros for critical review of the manuscript and excellent suggestions. Grant support during the writing of this review was received from the National Institutes of Health, Arthritis Foundation, and the Edward T. and Ellen K. Dryer Charitable Foundation. The author has no financial conflicts of interest related to publication of this article.

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  1. Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109-2200, USA

    Steven K. Lundy

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Lundy, S.K. Killer B lymphocytes: the evidence and the potential. Inflamm. Res. 58, 345–357 (2009). https://doi.org/10.1007/s00011-009-0014-x

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