Immunology

Affinity maturation of antibodies during an immune response is achieved by multiple rounds of somatic hypermutation and subsequent preferential selection of those B cells that express B cell receptors with improved binding characteristics for the antigen. The mechanism by which B cells are selected has been difficult to define because of the complexity of the reactions involved. Mathematical modelling enabled us to rule out long-held hypotheses and to suggest a novel coherent framework with which to explain B cell selection. Using agent-based simulations we showed that competition for scarce antigen was unlikely to drive B cell selection. Rather competition for T cell help could provide the required strong selective force. Recent experiments provide support for our model in which B cells compete for cytokines produced by follicular helper T cells that shape the affinity and isotype of the antibody response.

Selected References

• Batista FD, Iber D, Neuberger MS., B cells acquire antigen from target cells after synapse formation. Nature. (2001); 411:489-94.
• Iber D, Maini PK., A mathematical model for germinal centre kinetics and affinity maturation. J Theor Biol. (2002); 219:153-75.
• Iber D, Formation of the B cell synapse: Retention or Recruitment? Cell Mol Life Sci. (2005); 62:206-13.
• Iber D, Gruhn, T, Organization of B cell receptors on the cell membrane , IEE Proc Systems Biol (2006); 153, 401-404
• Meyer-Herrmann M, Maini PK, Iber D, An analysis of B cell selection mechanisms in germinal centres. Math. Med. Biol. (2006); 23, 255-77
• Lee Reinhardt R, Liang, H-E,  Locksley, RM, Cytokine-secreting follicular T cells shape the antibody repertoire, Nat Immunology (2009); 10: 385-393
  

Book Chapters

• Beale R, Iber D, Somatic evolution of antibody genes. Chapter 10 in The Implicit Genome, Editor L.H. Caporale, Oxford University Press (2006)