The biology of the germinal center

The immune system requires the production of high affinity antibodies of different subclasses to accomplish its many effector functions. Specific steps in B-cell ontogeny that occur within germinal centers of secondary lymphoid organs create much of the diversity in the immune system. This process also provides the raw material for the genesis of B-cell lymphomas as misdirection of the molecular machinery that regulate these steps can cause chromosomal translocations, prevent apoptosis and promote proliferation of abnormal clones. Many recent avenues of investigation have elucidated that the germinal center is a dynamic microenvironment where B-cells undergo repeated rounds of mutation and selection. Gene expression studies have further shown that malignancies derived from germinal center B-cells elaborate specific gene expression signatures that derive from neoplastic cells as well as elements of the host response such as T-cells and macrophages. This review will examine the current understanding of B-cell development in the germinal center and the key molecules involved in this process. Interactions between lymphoma cells and their cellular partners and models in the growth and development of follicular lymphoma will be presented.