ANTIBODY AFFINITY MATURATION
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.
PUBLICATIONS:
PUBLICATIONS:
- Meyer-Hermann ME, Maini PK, Iber D
An analysis of B cell selection mechanisms in germinal centers.
Math Med Biol (2006) 23, 255-77 - Iber D, Gruhn T
Organisation of B-cell receptors on the cell membrane.
Syst Biol (2006) 153, 401-4.
- Iber, D
Formation of the B cell synapse: retention or recruitment?
Cell Mol Life Sci (2005) 62, 206-13. - Iber D, Maini PK
A mathematical model for germinal centre kinetics and affinity maturation.
J Theor Biol (2002) 219, 153-75 - Batista FD, Iber D, Neuberger MS
B cells acquire antigen from target cells after synapse formation.
Nature (2001) 411, 489-94.
- Beale R and Iber D
Somatic evolution of antibody genes.
Chapter 10 in The Implicit Genome, Editor L.H. Caporale, Oxford University Press, 2006