Functional anatomy of germinal centers

This year we celebrate the first centennial of the discovery of germinal centers by Flemming in 1884. The present paper reviews and adds new data to the functional anatomy of a germinal center. Emphasizing its reactive nature, we first describe a germinal center reaction and then deal with its infrastructural aspects and constituent cell populations, both lymphoid and nonlymphoid. Elements involved in the de novo formation of a germinal center, like antigen, T cells, and the mysterious germinal-center-precursor cell, are discussed. Next, attention is paid to the requirements for lymphoid cells to migrate into germinal centers, and novel features of germinal-center-seeking cells are presented. Subsequently, we discuss kinetic aspects of the high proliferative activity in a germinal center; and finally a description of the functional capacities of germinal-center-derived cells, such as B memory cells and IgM-antibody-forming cell precursors, completes this picture of present-day knowledge of the germinal center, a structure which has yet to reveal its last secrets.