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PMID: 16630024 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Type I cytokine profiles of human naïve and memory B lymphocytes: a potential for memory cells to impact polarization.

Immunology ·Vol. 118 ·No. 1 ·2006-05-00 ·Pages 66-77

Gagro A, Servis D, Cepika AM, Toellner KM, Grafton G, Taylor DR, Branica S, Gordon J

Abstract

B cells bifurcating along 'type 1' or 'type 2' pathways under the influence of polarizing cytokines can, in turn, influence the direction of an immune response. Here, we compare the capacity of human B cells residing within naïve and memory compartments to participate in type 1 polarizing responses. B-cell receptor (BCR) engagement provided the main signal for interleukin (IL)-12Rbeta1 expression in the two subsets: this was potentiated by CD154 together with interferon-gamma (IFN-gamma) but inhibited by IL-12. IL-12Rbeta2 could be induced on a minority of B cells by the same signals, and also by IFN-gamma alone. WSX-1, a receptor for IL-27, was expressed in both subsets with no evidence for its regulation by the signals studied. While neither subset was capable of secreting much IL-12 p70, memory B cells could produce a small amount of IL-12 p40 on CD40 ligation. Memory B cells also, exclusively, expressed IL-23 p19 mRNA on BCR triggering. Importantly, products of appropriately stimulated memory--but not naive--B cells were shown to promote the synthesis of IFN-gamma in uncommitted T-helper cells. The data indicate an equal capacity for naïve and memory B cells to respond within a type 1 polarizing environment. Although poorly equipped for initiating type 1 responses, B cells--by virtue of the memory subset--reveal a capacity for their maintenance and amplification following T-dependent signalling.

MeSH Terms
B-Lymphocyte Subsets/immunology CD40 Antigens/immunology Cell Differentiation/immunology Cells, Cultured Cytokines/biosynthesis Enzyme-Linked Immunosorbent Assay/methods Humans Immunologic Memory Interferon-gamma/biosynthesis Interleukin-12/biosynthesis Interleukin-17/metabolism Interleukin-23 Interleukin-23 Subunit p19 Interleukins/biosynthesis Lymphocyte Cooperation/immunology Receptors, Antigen, B-Cell/immunology Receptors, Interleukin/metabolism Receptors, Interleukin-12 Reverse Transcriptase Polymerase Chain Reaction/methods Signal Transduction/immunology T-Lymphocytes, Helper-Inducer/immunology
Chemicals
CD40 Antigens Cytokines IL17D protein, human IL23A protein, human Interleukin-17 Interleukin-23 Interleukin-23 Subunit p19 Interleukins Receptors, Antigen, B-Cell Receptors, Interleukin Receptors, Interleukin-12 Interleukin-12 Interferon-gamma
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gagro Alenka
Institute of Immunology, Zagreb, Croatia. [email protected]
Servis Drazen
Cepika Alma-Martina
Toellner Kai-Michael
Grafton Gillian
Taylor Dale R
Branica Srecko
Gordon John
References (45)
45 references, click to expand
  1. 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
  2. Autocrine regulation of IL-12 receptor expression is independent of secondary IFN-gamma secretion and not restricted to T and NK cells.
    J Immunol. 1999 Nov 15;163(10):5257-64 PMID: 10553047
  3. B cells solicit their own help from T cells.
    J Exp Med. 1996 Mar 1;183(3):891-9 PMID: 8642293
  4. IL-4-dependent IgE switch in membrane IgA-positive human B cells.
    J Immunol. 1991 Nov 1;147(9):3001-4 PMID: 1919002
  5. Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness.
    J Immunol. 1998 Sep 15;161(6):2723-30 PMID: 9743329
  6. Characterization of IL-12 receptor beta1 chain (IL-12Rbeta1)-deficient mice: IL-12Rbeta1 is an essential component of the functional mouse IL-12 receptor.
    J Immunol. 1997 Aug 15;159(4):1658-65 PMID: 9257825
  7. Distinct profiles of human B cell effector cytokines: a role in immune regulation?
    J Immunol. 2004 Mar 15;172(6):3422-7 PMID: 15004141
  8. Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes.
    J Immunol. 1998 Sep 1;161(5):2223-31 PMID: 9725215
  9. Cytokine regulation of IL-12 receptor beta2 expression: differential effects on human T and NK cells.
    Eur J Immunol. 2000 May;30(5):1364-74 PMID: 10820383
  10. Th2 activities induced during virgin T cell priming in the absence of IL-4, IL-13, and B cells.
    J Immunol. 2002 Sep 15;169(6):2900-6 PMID: 12218103
  11. IL-12p40-dependent agonistic effects on the development of protective innate and adaptive immunity against Salmonella enteritidis.
    J Immunol. 2001 Nov 1;167(9):5304-15 PMID: 11673546
  12. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells.
    Immunity. 2002 Jun;16(6):779-90 PMID: 12121660
  13. Interferon-gamma and interleukin-4 regulate T cell interleukin-12 responsiveness through the differential modulation of high-affinity interleukin-12 receptor expression.
    Eur J Immunol. 1997 Mar;27(3):647-52 PMID: 9079804
  14. Induction of IgG2a class switching in B cells by IL-27.
    J Immunol. 2004 Aug 15;173(4):2479-85 PMID: 15294962
  15. Human non-germinal center B cell interleukin (IL)-12 production is primarily regulated by T cell signals CD40 ligand, interferon gamma, and IL-10: role of B cells in the maintenance of T cell responses.
    J Exp Med. 1999 Jan 4;189(1):1-12 PMID: 9874559
  16. Accessory molecule regulation of naive CD4 T cell activation.
    Immunol Res. 1996;15(2):114-25 PMID: 8839780
  17. In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment.
    Blood. 2003 Dec 1;102(12):4084-9 PMID: 12893768
  18. Dendritic cells and the control of immunity.
    Nature. 1998 Mar 19;392(6673):245-52 PMID: 9521319
  19. Naive and memory B cells respond differentially to T-dependent signaling but display an equal potential for differentiation toward the centroblast-restricted CD77/globotriaosylceramide phenotype.
    Eur J Immunol. 2003 Jul;33(7):1889-98 PMID: 12811849
  20. HL60 cells halted in G1 or S phase differentiate normally.
    Exp Cell Res. 2002 Nov 15;281(1):28-38 PMID: 12441127
  21. Regulation of interleukin-12 receptor beta1 chain expression and interleukin-12 binding by human peripheral blood mononuclear cells.
    Eur J Immunol. 1997 Jan;27(1):147-54 PMID: 9022011
  22. The IL-12Rbeta2 gene functions as a tumor suppressor in human B cell malignancies.
    J Clin Invest. 2004 Jun;113(11):1651-9 PMID: 15173892
  23. Cholera toxin suppresses interleukin (IL)-12 production and IL-12 receptor beta1 and beta2 chain expression.
    J Exp Med. 1999 Feb 1;189(3):541-52 PMID: 9927516
  24. IL-12p70-dependent Th1 induction by human B cells requires combined activation with CD40 ligand and CpG DNA.
    J Immunol. 2004 Jan 15;172(2):954-63 PMID: 14707068
  25. Antigen-primed T cells from B cell-deficient JHD mice fail to provide B cell help.
    J Immunol. 1998 Feb 15;160(4):1694-700 PMID: 9469426
  26. The interplay between T helper subset cytokines and IL-12 in directing human B lymphocyte differentiation.
    Eur J Immunol. 1999 Oct;29(10):3369-79 PMID: 10540349
  27. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.
    Immunity. 2000 Nov;13(5):715-25 PMID: 11114383
  28. Biological function and distribution of human interleukin-12 receptor beta chain.
    Eur J Immunol. 1996 Feb;26(2):345-50 PMID: 8617302
  29. Reciprocal regulation of polarized cytokine production by effector B and T cells.
    Nat Immunol. 2000 Dec;1(6):475-82 PMID: 11101868
  30. Dendritic cells and resting B cells form clusters in vitro and in vivo: T cell independence, partial LFA-1 dependence, and regulation by cross-linking surface molecules.
    J Immunol. 1998 Feb 15;160(4):1774-81 PMID: 9469436
  31. IL-12: the role of p40 versus p75.
    Scand J Immunol. 2002 Jul;56(1):1-11 PMID: 12100467
  32. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity.
    Annu Rev Immunol. 1995;13:251-76 PMID: 7612223
  33. IL-23: a cytokine that acts on memory T cells.
    Sci STKE. 2002 Jan 08;2002(114):pe1 PMID: 11784889
  34. B cells capturing antigen conjugated with CpG oligodeoxynucleotides induce Th1 cells by elaborating IL-12.
    J Immunol. 2002 Jul 15;169(2):787-94 PMID: 12097381
  35. The immunoglobulin class switch: beyond "accessibility".
    Immunity. 1997 Mar;6(3):217-23 PMID: 9075922
  36. Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12 receptor beta 2 expression.
    J Immunol. 2002 Jun 15;168(12):6165-72 PMID: 12055229
  37. Regulation of the IL-12/IL-12R axis: a critical step in T-helper cell differentiation and effector function.
    Immunol Rev. 1999 Aug;170:65-72 PMID: 10566142
  38. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.
    J Immunol. 2002 Jun 1;168(11):5699-708 PMID: 12023369
  39. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits.
    Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14002-7 PMID: 8943050
  40. IL-12 receptor. II. Distribution and regulation of receptor expression.
    J Immunol. 1992 May 15;148(10):3125-32 PMID: 1578139
  41. Role of IL-12 in human B lymphocyte proliferation and differentiation.
    J Immunol. 1995 Feb 15;154(4):1606-13 PMID: 7836745
  42. Switch circles from IL-4-directed epsilon class switching from human B lymphocytes. Evidence for direct, sequential, and multiple step sequential switch from mu to epsilon Ig heavy chain gene.
    J Immunol. 1994 Apr 1;152(7):3427-35 PMID: 8144926
  43. B cells regulate autoimmunity by provision of IL-10.
    Nat Immunol. 2002 Oct;3(10):944-50 PMID: 12244307
  44. Expression and function of IL-12 and IL-18 receptors on human tonsillar B cells.
    J Immunol. 2000 Dec 15;165(12):6880-8 PMID: 11120812
  45. Development of Th1-type immune responses requires the type I cytokine receptor TCCR.
    Nature. 2000 Oct 19;407(6806):916-20 PMID: 11057672
Article Info
Journal
Immunology
Abbr.
Immunology
ISSN
0019-2805
Published
2006-05-00
Pages
66-77
Language
English
Region
England
NLM ID
0374672
PMCID
PMC1782263
Subset
IM
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