Cell interaction molecules and cytokines which participate in B lymphopoiesis

A molecular and cellular definition of the bone marrow microenvironment is rapidly contributing to our understanding of lymphohaemopoiesis. While lineage specific genes and their protein products are being identified, information is accumulating about mechanisms which may regulate their expression. Stimulation of B lymphocyte precursor replication, and other discrete functions, are being attributed to cytokines such as interleukin 7 (IL-7). The activity of these factors may be controlled at the level of synthesis, local concentration and interaction with extracellular matrix. Extremely small amounts of IL-7 are made by stromal cells, which are themselves being thoroughly studied as cloned cell lines. This in vitro characterization suggests that stromal cells can make at least 12 cytokines, that they can respond to some of those cytokines themselves, and that they retain differentiation potential. Several molecules have been identified which are probably required for recognition between cells in marrow. It is noteworthy that they belong to several previously described families of adhesion molecules and none is unique to that tissue. VCAM-1 is constitutively expressed on stromal cells in marrow and can be recognized by pre-B cells which bear the integrin VLA-4. The same pair of molecules is probably responsible for extravasation of leukocytes in other tissues during inflammation. Cell adhesion molecules are likely to work in a carefully coordinated and cooperative fashion. Their activity can be controlled by expression or, in some cases, modulated after display on the cell surface. For example, while most haemopoietic cells bear CD44, only certain cells utilize it for recognition of the ligand hyaluronate. The affinity for hyaluronate can be experimentally regulated and depends on the cytoplasmic domain of CD44. This capability for dynamic change may be important for transient interactions between cells, permitting movement of maturing precursors within and from marrow.