Antigen first activates T and B lymphocytes in the T-cell areas of secondary lymphoid tissues where cognate-and costimulus-dependent proliferation expands the population of reactive lymphocytes. Selected T-and B-cell progeny from this population migrate into B-cell zones to form germinal centers (GC), where intense proliferation, apoptosis, and V (D) J hypermutation takes place. It is now known that each of these processes occur in both compartments of GC lymphocytes and that the GC T-cell represents an unusual Thy-1–subset of α T-helper cells that may represent a terminally differentiated cell that is lost with the end of the GC reaction.