The Role of Chemokines in Regulating Cell Migration during Humoral Immune Responses

Three major types of hematopoietic cells cooperate in the recognition of antigens in humoral adaptive immune responses: T lymphocytes, B lymphocytes, and antigen-presenting cells (APC). All three types of cells originate from pluripotent hematopoietic stem cells (HSC), are made in the primary lymphoid organs (bone marrow and thymus), and are used for immune responses in secondary lymphoid organs (spleen, lymph nodes, and the gut-associated lymphoid tissues), and in nonlymphoid tissues. The essence of a properly functioning immune system is the high degree of cell motility during cell maturation and immune responses. Cell migration is controlled by multistep processes that include chemoattraction, cell-cell adhesion and, where needed, transmigration through cell layers (Springer, 1994; Butcher et al., 1999). In this review we will consider the trafficking of cells cooperating in the development of the immune system and in a humoral immune response. We will focus our attention on the role(s) of chemokines and their receptors during these processes. The importance of chemokines (which are classified on the basis of the number and spacing of NH sub(2)-terminal cysteins into C, CC, CXC, and CX sub(3)C chemokines) and their receptors in the microanatomical structuring of lymphoid organs has been established (for a recent review see Zlotnik et al., 1999), but the role of each chemokine in regulating immune cell development and immune responses is far from understood. Several chemokines and their receptors are candidates for controlling the migration of lymphocytes within primary lymphoid organs, from primary to secondary lymphoid organs and, during a humoral immune response, within and between secondary lymphoid organs. Most of them have only been characterized by their expression and by chemotactic activities measured in vitro. For only a few has it been possible to determine their function in vivo either by naturally occurring defects or by targeted inactivation of the chemokine or chemokine receptor genes. This lack of functional insight is likely to be a consequence of redundancy in the system. One chemokine can have more than one receptor, one receptor can recognize more than one chemokine, one cell can produce more than one chemokine, and several different types of cells can produce either the same chemokine or the same chemokine receptor.