SEX-HORMONES AS NEGATIVE REGULATORS OF LYMPHOPOIESIS

B lymphocytes, together with cells of seven other lineages, are made i n large numbers from precursors in the bone marrow. Using cell culture models and recombinant proteins, progress has been rapid in identifyi ng cytokines which could potentially regulate the proliferation, diffe rentiation and migration of B-cell precursors. However, we still know little about molecular mechanisms which are important for maintaining steady-state conditions in vivo. B lymphopoiesis is severely diminishe d during pregnancy in normal mice and this provided a clue that sex ho rmones might be important negative regulators. Administration of estro gens alone, or in combination with progesterone, preferentially suppre ssed IL-7 responding cells and their progeny in bone marrow. There is precedent for these observations in the thymus, which transiently invo lutes during pregnancy, and also atrophies following estrogen treatmen t. The actual mechanism(s) through which sex steroids influence lympho poiesis remain unclear, but cell culture experiments should be informa tive about potential interactions between hormones, the bone marrow mi croenvironment, and lymphocyte precursors. These findings raise a numb er of other important issues. For example, we need to learn if sex ste roids are produced and/or concentrated locally within the marrow, if h uman lymphopoiesis is sensitive to these hormones, and if production o f lymphocytes can be augmented in aging and in immunodeficiency by hor mone manipulation.