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 alpha beta T-helper cells that may represent a terminally differentiated cell that is lost with the end of the GC reaction.