Home LiteratureArticle Details
PMID: 7516405 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory.

The Journal of experimental medicine ·Vol. 180 ·No. 1 ·1994-07-01 ·Pages 157-63

Foy TM, Laman JD, Ledbetter JA, Aruffo A, Claassen E, Noelle RJ

Abstract

gp39, the ligand for CD40 expressed on activated CD4+ T helper cells, is required for the generation of antibody responses to T-dependent (TD) antigens. Treatment of mice with anti-gp39 in vivo inhibits both primary and secondary antibody formation to TD, but not T-independent antigens. However, the role of this receptor-ligand pair in the development of germinal centers and the generation of B cell memory is as yet undefined. Using an antibody to gp39, this study examines the in vivo requirement for gp39-CD40 interactions in the induction of germinal center formation, as well as in the generation of B cell memory. Animals were immunized, treated in vivo with anti-gp39, and evaluated using immunohistochemical staining for the presence of splenic germinal centers 9-11 d after immunization. The results demonstrate that the formation of germinal centers was completely inhibited as a result of treatment with anti-gp39. Moreover, adoptive transfer experiments demonstrate that the generation of antigen-specific memory B cells is also inhibited as a consequence of blocking gp39-CD40 interactions. Taken together, the data demonstrate that gp39-CD40 interactions are critical not only for the generation of antibody responses, but also in the development of B cell memory.

MeSH Terms
Animals Antibody Formation Antigens, CD/physiology Antigens, Differentiation, B-Lymphocyte/physiology B-Lymphocytes/immunology CD40 Antigens CD40 Ligand Female Immunologic Memory Membrane Glycoproteins/physiology Mice Mice, Inbred BALB C
Chemicals
Antigens, CD Antigens, Differentiation, B-Lymphocyte CD40 Antigens Membrane Glycoproteins CD40 Ligand
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Foy T M
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756.
Laman J D
Ledbetter J A
Aruffo A
Claassen E
Noelle R J
References (42)
42 references, click to expand
  1. CD40 is functionally expressed on human thymic epithelial cells.
    J Immunol. 1992 Aug 1;149(3):775-82 PMID: 1378865
  2. Effect of thymus cell injections on germinal center formation in lymphoid tissues of nude (thymusless) mice.
    Cell Immunol. 1974 Sep;13(3):416-30 PMID: 4217657
  3. Monoclonal antibodies specific for novel murine cell surface markers define subpopulations of germinal center cells.
    Cell Immunol. 1992 Sep;143(2):449-66 PMID: 1511484
  4. The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity.
    EMBO J. 1992 Dec;11(12):4313-21 PMID: 1385114
  5. Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help.
    J Immunol. 1992 Dec 15;149(12):3817-26 PMID: 1281189
  6. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome.
    Cell. 1993 Jan 29;72(2):291-300 PMID: 7678782
  7. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM.
    Nature. 1993 Feb 11;361(6412):539-41 PMID: 7679206
  8. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM.
    Nature. 1993 Feb 11;361(6412):541-3 PMID: 8094231
  9. CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome.
    Science. 1993 Feb 12;259(5097):990-3 PMID: 7679801
  10. Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2170-3 PMID: 7681587
  11. CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40.
    J Exp Med. 1993 Aug 1;178(2):669-74 PMID: 7688031
  12. Induction of human IgE synthesis in B cells by mast cells and basophils.
    Nature. 1993 Sep 23;365(6444):340-3 PMID: 7690905
  13. In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines, and antibody production delineates sites of cognate T-B cell interactions.
    J Exp Med. 1993 Nov 1;178(5):1555-65 PMID: 7693849
  14. In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II. Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39.
    J Exp Med. 1993 Nov 1;178(5):1567-75 PMID: 7693850
  15. B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells.
    J Exp Med. 1994 Mar 1;179(3):819-30 PMID: 7509361
  16. Memory B cell development but not germinal center formation is impaired by in vivo blockade of CD40-CD40 ligand interaction.
    J Exp Med. 1994 Jul 1;180(1):141-55 PMID: 7516404
  17. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens.
    Curr Top Microbiol Immunol. 1978;81:115-20 PMID: 567555
  18. A hybridoma secreting IgM anti-Iglb allotype.
    Curr Top Microbiol Immunol. 1978;81:37-9 PMID: 567562
  19. The generation of memory cells. II. Generation of B memory cells with preformed antigen-antibody complexes.
    Immunology. 1978 Apr;34(4):643-52 PMID: 309848
  20. Peanut lectin binding properties of germinal centres of mouse lymphoid tissue.
    Nature. 1980 Mar 27;284(5754):364-6 PMID: 7360273
  21. Mouse lymph node germinal centers contain a selected subset of T cells--the helper phenotype.
    J Immunol. 1982 May;128(5):2243-6 PMID: 6120978
  22. Germinal centre B cells: antigen specificity and changes in heavy chain class expression.
    Nature. 1982 Jul 22;298(5872):377-9 PMID: 6806671
  23. Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation.
    J Immunol. 1982 Dec;129(6):2698-707 PMID: 6982940
  24. Relationship of germinal centers in lymphoid tissue to immunologic memory. VI. Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin.
    J Immunol. 1983 Nov;131(5):2254-7 PMID: 6605381
  25. Somatic mutation and the maturation of immune response to 2-phenyl oxazolone.
    Nature. 1984 Nov 15-21;312(5991):271-5 PMID: 6504141
  26. Molecular events during maturation of the immune response to oxazolone.
    Nature. 1985 Aug 1-7;316(6027):412-8 PMID: 3927173
  27. Preparation and analysis of antigen-specific memory B cells.
    J Immunol. 1985 Dec;135(6):3777-84 PMID: 2415585
  28. Antigen-driven selection of virgin and memory B cells.
    Immunol Rev. 1986 Jun;91:61-85 PMID: 3089914
  29. Germinal centers develop oligoclonally.
    Eur J Immunol. 1987 Jul;17(7):1069-72 PMID: 3301368
  30. Thymus-dependent antigenic stimulation of hapten-specific B lymphocytes.
    Immunol Rev. 1987 Oct;99:173-92 PMID: 2445657
  31. Selective survival and expression of B-lymphocyte memory cells during long-term serial transplantation.
    Cell Immunol. 1987 Dec;110(2):226-32 PMID: 3500794
  32. A role for mature B cells in bone marrow transplantation.
    Immunology. 1988 May;64(1):147-53 PMID: 3290093
  33. Mechanism of antigen-driven selection in germinal centres.
    Nature. 1989 Dec 21-28;342(6252):929-31 PMID: 2594086
  34. Primary antibody-forming cells and secondary B cells are generated from separate precursor cell subpopulations.
    Cell. 1989 Dec 22;59(6):1049-59 PMID: 2598260
  35. Does the availability of either B cells or CD4+ cells limit germinal centre formation?
    Immunology. 1990 Mar;69(3):487-9 PMID: 1968890
  36. Germinal center reaction and B lymphocytes: morphology and function.
    Curr Top Pathol. 1990;84 ( Pt 1):103-48 PMID: 2292191
  37. Germinal center B cells and antibody production in the bone marrow.
    J Immunol. 1991 Jun 15;146(12):4071-7 PMID: 2040791
  38. Germinal centres and the immune response. 37th Forum in Immunology.
    Res Immunol. 1991 Mar-Apr;142(3):219-82 PMID: 1680242
  39. Growing human B lymphocytes in the CD40 system.
    Nature. 1991 Oct 17;353(6345):678-9 PMID: 1717852
  40. Immunodeficiency with hyper-IgM (HIM).
    Immunodefic Rev. 1992;3(2):101-21 PMID: 1554497
  41. De novo germinal center formation.
    Immunol Rev. 1992 Apr;126:77-98 PMID: 1597322
  42. A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells.
    Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6550-4 PMID: 1378631
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1994-07-01
Pages
157-63
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191546
Subset
IM
Grants
NIAID NIH HHS · AI-26296 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]