TNFR molecules - continued

We have produced the ligand for a second TNFR family member, CD40, in a biologically active soluble form. This has proved effective in maintaining differentiating primary B cells in culture for the first time. This has opened up exciting new opportunities for analysing the factors that control the numbers of antibody producing cells at specific sites where they can effectively tackle invading viruses.

Costimulatory molecules

We have cloned the genes encoding the major costimulatory ligands, CD80, CD86 and LICOS, and their receptors, CD28, CTLA4 and ICOS, and have produced them as soluble proteins, against which we have prepared antibodies. We are using them in studies of the crucial costimulatory functions of antigen-presenting dendritic cells that are the central co-ordinators of the immune response. The molecules have some unusual structural features that are likely to affect their interactions. Details of the biophysical parameters of the ligand-receptor interactions are presently under investigation (figure2).

Other studies

The group have also been involved in the analysis of genetic differences in responses to a number of infections using microarray analysis of gene expression (figure 3).

Publications:

  • Tregaskes CA, Glansbeek HL, Gill AC, Hunt LG, Burnside J, Young JR. (2005) Conservation of biological properties of the CD40 ligand, CD154 in a non-mammalian vertebrate. Dev Comp Immunol 29:361-374. [Abstract]. 
  • Withers DR, Davison TF, Young JR. (2005) Developmentally programmed expression of AID in chicken B cells. Dev. Comp. Immunol. 29:651-662. [Abstract]. 
  • Withers DR, Young JR, Davison TF. (2005) Infectious bursal disease virus-induced immunosuppression in the chick is associated with the presence of undifferentiated follicles in the recovering bursa. Viral Immunology 18:128-138. [Abstract]. 
  • Withers, DR, Davison, TF and Young JR. (2006) Diversified bursal medullary B cells survive and expand independently after depletion following neonatal infectious bursal disease virus infection. Immunology. 117:558-565. [Abstract]. 
  • Ruby, T, Whittaker, C, Withers, DR, Chelbi-Alix, MK, Morin, V, Oudin A, Young, JR and Zoorob, R. (2006) Transcriptional Profiling Reveals a Possible Role for the Timing of the Inflammatory Response in Determining Susceptibility to a Viral Infection. J. Virol. 80: 9207-9216. [Abstract].