Somatic hypermutation and B-cell malignancies.

Abstract

During a follicle centre response, the immunoglobulin genes are subjected to a hypermutation mechanism which introduces predominantly single base changes, non-randomly, into the immunoglobulin V region (IgV) genes. B cells with mutated IgV genes are then selected according to the affinity of the encoded antibody for antigen retained on the follicular dendritic cells, resulting in an increase in the affinity of the humoral response. The identification of mutated immunoglobulin genes has been applied to the study of normal B cells and B-cell lymphomas to determine either follicle centre cell ancestry, or continued influence of the follicle centre microenvironment. Although analysis of mutations in many lymphomas has confirmed previous hypotheses, there have been some surprises, such as the identification of rearranged and mutated IgV genes in Hodgkin's Reed-Sternberg cells. In this mini-review we will examine the characteristics of the hypermutation mechanism and the way in which mutations in IgV genes have been used to study B-cell malignancies.