SEX-HORMONES AS NEGATIVE REGULATORS OF LYMPHOPOIESIS

B lymphocytes, together with cells of seven other lineages, are made in large numbers from precursors in the bone marrow. Using cell culture models and recombinant proteins, progress has been rapid in identifying cytokines which could potentially regulate the proliferation, differentiation 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 diminished during pregnancy in normal mice and this provided a clue that sex hormones might be important negative regulators. Administration of estrogens alone, or in combination with progesterone, preferentially suppressed IL-7 responding cells and their progeny in bone marrow. There is precedent for these observations in the thymus, which transiently involutes during pregnancy, and also atrophies following estrogen treatment. The actual mechanism(s) through which sex steroids influence lymphopoiesis remain unclear, but cell culture experiments should be informative about potential interactions between hormones, the bone marrow microenvironment, and lymphocyte precursors. These findings raise a number of other important issues. For example, we need to learn if sex steroids are produced and/or concentrated locally within the marrow, if human lymphopoiesis is sensitive to these hormones, and if production of lymphocytes can be augmented in aging and in immunodeficiency by hormone manipulation.