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PMID: 19249230 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus.

Immunity ·Vol. 30 ·No. 3 ·2009-03-20 ·Pages 421-33

Wojciechowski W, Harris DP, Sprague F, Mousseau B, Makris M, Kusser K, Honjo T, Mohrs K, Mohrs M, Randall T, Lund FE

Abstract

Immunity to the intestinal parasite Heligomosomoides polygyrus is dependent on the successful generation of T helper 2 (Th2) memory cells. We showed that B cells contribute to immunity against H. polygyrus by producing antibody (Ab) and by promoting expansion and differentiation of primary and memory Th2 cells. We also demonstrated that cytokine-producing effector B cells were essential for effective immunity to H. polygyrus. Tumor necrosis factor alpha production by B cells was necessary for sustained Ab production, whereas interleukin 2 production by B cells was necessary for Th2 cell expansion and differentiation. These results show that B cells mediate protection from pathogens not only by presenting antigen and secreting antibody but also by producing cytokines that regulate the quality and magnitude of humoral and cellular immune responses.

MeSH Terms
Animals Antibody Formation Antigens, Helminth/immunology B-Lymphocytes/immunology Cytokines/metabolism Enzyme-Linked Immunosorbent Assay Immunity, Cellular Interleukin-4/metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Nematospiroides dubius/immunology Strongylida Infections/immunology,prevention & control Th2 Cells/immunology
Chemicals
Antigens, Helminth Cytokines Interleukin-4
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Wojciechowski Wojciech
Trudeau Institute, Saranac Lake, NY 12983, USA.
Harris David P
Sprague Frank
Mousseau Betty
Makris Melissa
Kusser Kim
Honjo Tasuko
Mohrs Katja
Mohrs Markus
Randall Troy
Lund Frances E
References (52)
52 references, click to expand
  1. B cells play a regulatory role in mice infected with the L3 of Brugia pahangi.
    Int Immunol. 2005 Apr;17(4):373-82 PMID: 15724063
  2. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice.
    Nature. 1988 Aug 25;334(6184):676-82 PMID: 3261841
  3. The sequential role of lymphotoxin and B cells in the development of splenic follicles.
    J Exp Med. 1998 Apr 6;187(7):997-1007 PMID: 9529316
  4. Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites.
    Nat Med. 2006 Aug;12(8):955-60 PMID: 16892038
  5. B cells modulate T cells so as to favour T helper type 1 and CD8+ T-cell responses in the acute phase of Trypanosoma cruzi infection.
    Immunology. 2007 Dec;122(4):584-95 PMID: 17635611
  6. Organogenic role of B lymphocytes in mucosal immunity.
    Science. 1999 Dec 3;286(5446):1965-8 PMID: 10583962
  7. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion.
    J Exp Med. 1998 Apr 6;187(7):1009-18 PMID: 9529317
  8. Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo.
    Immunol Rev. 2004 Oct;201:57-74 PMID: 15361233
  9. Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor alpha, and Th2 cells.
    J Immunol. 2005 Dec 1;175(11):7103-7 PMID: 16301612
  10. AID-/-mus-/- mice are agammaglobulinemic and fail to maintain B220-CD138+ plasma cells.
    J Immunol. 2007 Feb 15;178(4):2192-203 PMID: 17277124
  11. Splenic T zone development is B cell dependent.
    J Exp Med. 2001 Dec 3;194(11):1649-60 PMID: 11733579
  12. Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo.
    J Exp Med. 2003 Apr 7;197(7):875-83 PMID: 12668647
  13. Protective immune mechanisms in helminth infection.
    Nat Rev Immunol. 2007 Dec;7(12):975-87 PMID: 18007680
  14. Transfer of immunity to Nematospiroides dubius: co-operation between lymphoid cells and antibodies in mediating worm expulsion.
    Parasite Immunol. 1981 Autumn;3(3):249-59 PMID: 7301409
  15. Innate responses of B cells.
    Eur J Immunol. 2007 Dec;37(12):3304-10 PMID: 18000957
  16. Regulation of IFN-gamma production by B effector 1 cells: essential roles for T-bet and the IFN-gamma receptor.
    J Immunol. 2005 Jun 1;174(11):6781-90 PMID: 15905519
  17. The role of B cells in the development of CD4 effector T cells during a polarized Th2 immune response.
    J Immunol. 2007 Sep 15;179(6):3821-30 PMID: 17785819
  18. B lymphocytes regulate dendritic cell (DC) function in vivo: increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation.
    J Exp Med. 2000 Aug 21;192(4):475-82 PMID: 10952717
  19. Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus.
    J Exp Med. 2008 Dec 22;205(13):3041-52 PMID: 19047439
  20. Production of cytokines by human B cells in health and disease.
    Immunol Today. 1997 Jul;18(7):343-50 PMID: 9238838
  21. Regulatory roles for cytokine-producing B cells in infection and autoimmune disease.
    Curr Dir Autoimmun. 2005;8:25-54 PMID: 15564716
  22. Interleukin 2 plays a central role in Th2 differentiation.
    Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3880-5 PMID: 15004274
  23. Reciprocal regulation of polarized cytokine production by effector B and T cells.
    Nat Immunol. 2000 Dec;1(6):475-82 PMID: 11101868
  24. The immune response to parasitic helminths: insights from murine models.
    Trends Immunol. 2003 May;24(5):269-77 PMID: 12738422
  25. Priming of CD4+ T cells and development of CD4+ T cell memory; lessons for malaria.
    Parasite Immunol. 2006 Jan-Feb;28(1-2):25-30 PMID: 16438673
  26. Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.
    PLoS One. 2008 Aug 21;3(8):e3033 PMID: 18716662
  27. The role of OX40 ligand interactions in the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus.
    J Immunol. 2003 Jan 1;170(1):384-93 PMID: 12496423
  28. Not always the bad guys: B cells as regulators of autoimmune pathology.
    Nat Rev Immunol. 2008 May;8(5):391-7 PMID: 18437156
  29. Infection of mice with Nematospiroides dubius: demonstration of neutrophil-mediated immunity in vivo in the presence of antibodies.
    Immunology. 1984 Sep;53(1):147-54 PMID: 6469285
  30. CD40, but not CD154, expression on B cells is necessary for optimal primary B cell responses.
    J Immunol. 2003 Dec 1;171(11):5707-17 PMID: 14634078
  31. Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells.
    J Immunol. 2006 Mar 15;176(6):3498-506 PMID: 16517718
  32. Antibodies and B cell memory in viral immunity.
    Immunity. 2007 Sep;27(3):384-92 PMID: 17892847
  33. Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter.
    Immunity. 2001 Aug;15(2):303-11 PMID: 11520464
  34. The role of B lymphocytes as antigen-presenting cells.
    Arch Immunol Ther Exp (Warsz). 2008 Mar-Apr;56(2):77-83 PMID: 18373241
  35. Cytokine-producing B lymphocytes-key regulators of immunity.
    Curr Opin Immunol. 2008 Jun;20(3):332-8 PMID: 18417336
  36. Anti-TNF-alpha and Th1 cytokine-directed therapies for the treatment of asthma.
    Curr Opin Allergy Clin Immunol. 2006 Feb;6(1):43-50 PMID: 16505611
  37. A case for regulatory B cells.
    J Immunol. 2006 Jan 15;176(2):705-10 PMID: 16393950
  38. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab.
    Arthritis Rheum. 2004 Aug;50(8):2580-9 PMID: 15334472
  39. A critical role for B cells in the development of memory CD4 cells.
    J Immunol. 2000 Nov 15;165(10):5558-65 PMID: 11067910
  40. Tumor necrosis factor alpha is a critical component of interleukin 13-mediated protective T helper cell type 2 responses during helminth infection.
    J Exp Med. 1999 Oct 4;190(7):953-62 PMID: 10510085
  41. Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses.
    PLoS Pathog. 2006 Jun;2(6):e58 PMID: 16789842
  42. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5513-7 PMID: 2062833
  43. Leishmania major-specific B cells are necessary for Th2 cell development and susceptibility to L. major LV39 in BALB/c mice.
    J Immunol. 2008 Apr 1;180(7):4825-35 PMID: 18354206
  44. Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models.
    Annu Rev Immunol. 1997;15:505-33 PMID: 9143698
  45. B cell lineage contributions to antiviral host responses.
    Curr Top Microbiol Immunol. 2008;319:41-61 PMID: 18080414
  46. B cells amplify IFN-gamma production by T cells via a TNF-alpha-mediated mechanism.
    J Immunol. 2007 Oct 1;179(7):4857-66 PMID: 17878385
  47. Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs.
    Immunity. 2005 Apr;22(4):467-77 PMID: 15845451
  48. B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection.
    J Immunol. 2006 May 15;176(10):6147-54 PMID: 16670323
  49. A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus.
    J Exp Med. 1999 May 17;189(10):1639-48 PMID: 10330443
  50. Mature follicular dendritic cell networks depend on expression of lymphotoxin beta receptor by radioresistant stromal cells and of lymphotoxin beta and tumor necrosis factor by B cells.
    J Exp Med. 1999 Jan 4;189(1):159-68 PMID: 9874572
  51. IL-2 is necessary for the progression of leishmaniasis in susceptible murine hosts.
    J Immunol. 1993 May 1;150(9):3924-31 PMID: 8473741
  52. Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM.
    J Immunol. 1998 May 15;160(10):4776-87 PMID: 9590224
Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
Published
2009-03-20
Epub
2009-00-26
Pages
421-33
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2745290
Subset
IM
Grants
NIAID NIH HHS · R01 AI068056-03 · United States
NIAID NIH HHS · AI-68056 · United States
NIAID NIH HHS · R01 AI068056-04 · United States
NIAID NIH HHS · R01 AI068056-05 · United States
NIAID NIH HHS · AI-50844 · United States
NIAID NIH HHS · R01 AI068056 · United States
NIAID NIH HHS · R01 AI050844 · United States
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