Kincade P W, Medina K L, Smithson G
Oklahoma Medical Research Foundation, Oklahoma City 73104.
Immunol Rev. 1994 Feb;137:119-34. doi: 10.1111/j.1600-065x.1994.tb00661.x.
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.
B淋巴细胞与其他七个谱系的细胞一起，大量由骨髓中的前体细胞产生。利用细胞培养模型和重组蛋白，在鉴定可能调节B细胞前体增殖、分化和迁移的细胞因子方面取得了迅速进展。然而，我们对体内维持稳态条件至关重要的分子机制仍然知之甚少。在正常小鼠怀孕期间，B淋巴细胞生成会严重减少，这提示性激素可能是重要的负调节因子。单独给予雌激素或与孕酮联合使用，会优先抑制骨髓中对IL-7有反应的细胞及其后代。在胸腺中也有这些观察结果的先例，胸腺在怀孕期间会短暂退化，在雌激素治疗后也会萎缩。性类固醇影响淋巴细胞生成的实际机制尚不清楚，但细胞培养实验应该能提供有关激素、骨髓微环境和淋巴细胞前体之间潜在相互作用的信息。这些发现引发了许多其他重要问题。例如，我们需要了解性类固醇是否在骨髓局部产生和/或浓缩，人类淋巴细胞生成是否对这些激素敏感，以及通过激素操纵是否可以在衰老和免疫缺陷状态下增加淋巴细胞的产生。
