B cells recruited into T cell-dependent antibody responses have the potential to increase the affinity of the antibody they produce through a process of somatic hypermutation of their rearranged immunoglobulin variable region genes. This process occurs during T-dependent antibody responses in structures known as germinal centres. Germinal centres develop in the follicles of the secondary lymphoid organs such as — Payer’s patches, lymph nodes, the splenic white pulp and tonsils. While the hypermutation process can produce B cells that have higher affinity antibody for the inducing antigen, it also results in cells that have less or no affinity for the antigen, or importantly, altered specificity, including auto-reactivity. A sophisticated antigen and CD4 T-dependent selection process has evolved that identifies those cells that have the highest affinity for the inducing antigen. Central to this selection is a built-in safety mechanism in which all the B cells that have undergone immunoglobulin-V-region hypermutation kill themselves through apoptosis, unless they receive positive selection signals: first by engaging antigen held on specialised follicular dendritic cells and secondly by processing and presenting this to CD4 T cells, located towards the edge of the germinal centre. Successful interaction with the follicular T cells triggers differentiation of the germinal centre B cell in one of three directions: to become: a plasma cell, a memory B cell or a cell that remains in the germinal centre and undergoes further rounds of proliferation and selection.