Hypermutation in Germinal Centres

Jose Faro
Instituto Gulbenkian de Ciência

This is the abstract of a talk prepared for the Oeiras Mathematical and Computational Biology Workshop. June 20, 2003, Instituto Gulbenkian de Ciência

Abstract: Germinal centres (GC) are highly organised multicellular structures that form, transiently, out of primary follicles in secondary lymphoid organs, during the immune response to thymus-dependent antigens (Ag). There Ag-specific B lymphocytes proliferate intensely. About 5-7 days after the initiation of the GC reaction, proliferating B cells initiate a high rate mutation process that is localised to heavy and light variable genes of the expressed immunoglobulins.

Mutated variable regions usually decrease the affinity of the antibody-Ag reactions. Only occasionally mutations increase that affinity. Since in GCs the Ag is limiting, Ag-specific B cells compete strongly for Ag binding. Because B cell survival in GCs requires activation by Ag, those B cells with antibodies with higher affinity will survive preferentially, leading to an increase of the average affinity (affinity maturation).

Different experimental systems have been developed to study those processes of hypermutation and affinity maturation. An unresolved issue is to what extent mutations are random or biased toward specific nucleotide sequences within the variable genes (hot spots). We have started to analyse this issue by developing both analytical and computer simulation models of the hypermutation process. We discuss how our present theoretical results compare with experimental data on the immune response to 2-phenyloxazolone in face of the model assumptions.

For more information contact Luis Rocha at rocha@indiana.edu
Last Modified: June 16, 2003