Role of activin A in negative regulation of normal and tumor B lymphocytes

Activin A, a member of the transforming growth factor beta superfamily, has a wide spread expression pattern and pleiotropic functions. in this overvi ew we summarize data that points to a role of activin A in negative regulat ion of B lineage lymphocytes. Experiments performed by us and by other grou ps revealed the capacity of activin A to cause apoptotic death of tumor mye loma cells, through mechanisms of cell cycle inhibition and antagonism with the survival signal of interleukin-6, ill vitro studies on B lymphocyte ge neration from bone marrow stem cells and use of human nasal polyps as a mod el of inflamed tissue further demonstrate an inhibitory role of activin A i n B cell spread and accumulation. These data are analyzed with respect to o ur model of tissue organization that we term the "restrictin model of cell growth regulation." This model assumes a morphogen-like role of activin A i n the hematopoietic: system, Thus, the relative concentration of biological ly functional activin Al in different parts of the tissue, may determine th e local B cell content and functional state of these cells within a specifi c microenvironment.