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Gene Review

CD40  -  CD40 molecule, TNF receptor superfamily...

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Disease relevance of TNFRSF5


High impact information on TNFRSF5

  • RESULTS: Intracellular mammalian DNA activated immature BMDCs, as determined by the up-regulation of CD40 and CD86 as well as by the production of significant quantities of type I IFN [2].
  • Ligation of CD40 on B cells increases their ability to present Ag and to activate MHC class II (MHC-II)-restricted T cells [3].
  • Thus, CD40 signaling enhances the efficiency with which APC activate T cells by at least two related, but distinct, mechanisms: an early stage characterized by aggregation of MHC-II and CD80 clusters, and a late stage in which a significant increase in CD80 expression is observed [3].
  • Shortly after CD40 ligation on a B cell line, MHC-II and CD80 progressively accumulated in cholesterol-enriched microdomains on the cell surface, which correlated with an initial enhancement in their Ag presentation ability [3].
  • CD40-induced aggregation of MHC class II and CD80 on the cell surface leads to an early enhancement in antigen presentation [3].

Biological context of TNFRSF5

  • This was not due to down-regulation of a number of recognized co-stimulatory molecules including CD80, CD86 and CD40 [4].
  • Overall, these findings suggest that activation of bovine B cells through BCR cross-linking yields an activation phenotype that differs substantially from that of B cells activated through CD40 [5].
  • DC infected with S. typhimurium up-regulated cell surface expression of major histocompatibility class I (MHC-I), MHC-II, CD40, CD80 and CD86 [6].

Anatomical context of TNFRSF5

  • Cloning, expression and biological function of the bovine CD40 homologue: role in B-lymphocyte growth and differentiation in cattle [7].
  • Our results indicate that many of the functions described for human and mouse CD40 are also conserved in the bovine but that differences in subset distribution of expression of the CD40 molecule in lymphoid cell types in cattle may impact on regulation of the early activation steps in the acquired immune response [7].
  • A member of this superfamily, the CD40 molecule plays an important role in the differentiation of B lymphocytes into effector cells and in early activation through cognate interaction with T lymphocytes [7].

Analytical, diagnostic and therapeutic context of TNFRSF5

  • Cross-linkage of CD40 on bovine B lymphocytes upon coculture with CD40L-transfected cells resulted in the increased production of secretory IgM and, to a lesser extent, of IgG [7].
  • Moreover, CD40 ligation induced a second, late, more sustained enhancement of Ag presentation, which correlates with a significant increase in CD80 expression by APC [3].
  • BMDC activation was determined by flow cytometry (CD40, CD86) [2].


  1. Activation of dendritic cells by liposomes prepared from phosphatidylinositol mannosides from Mycobacterium bovis bacillus Calmette-Guerin and adjuvant activity in vivo. Sprott, G.D., Dicaire, C.J., Gurnani, K., Sad, S., Krishnan, L. Infect. Immun. (2004) [Pubmed]
  2. Intracellular mammalian DNA stimulates myeloid dendritic cells to produce type I interferons predominantly through a toll-like receptor 9-independent pathway. Martin, D.A., Elkon, K.B. Arthritis Rheum. (2006) [Pubmed]
  3. CD40-induced aggregation of MHC class II and CD80 on the cell surface leads to an early enhancement in antigen presentation. Clatza, A., Bonifaz, L.C., Vignali, D.A., Moreno, J. J. Immunol. (2003) [Pubmed]
  4. Differential effects of bovine viral diarrhoea virus on monocytes and dendritic cells. Glew, E.J., Carr, B.V., Brackenbury, L.S., Hope, J.C., Charleston, B., Howard, C.J. J. Gen. Virol. (2003) [Pubmed]
  5. Activation of bovine B cells via surface immunoglobulin M cross-linking or CD40 ligation results in different B-cell phenotypes. Haas, K.M., Estes, D.M. Immunology (2000) [Pubmed]
  6. Differential response of bovine monocyte-derived macrophages and dendritic cells to infection with Salmonella typhimurium in a low-dose model in vitro. Norimatsu, M., Harris, J., Chance, V., Dougan, G., Howard, C.J., Villarreal-Ramos, B. Immunology (2003) [Pubmed]
  7. Cloning, expression and biological function of the bovine CD40 homologue: role in B-lymphocyte growth and differentiation in cattle. Hirano, A., Brown, W.C., Estes, D.M. Immunology (1997) [Pubmed]
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