Filipp D, Alizadeh-Khiavi K, Richardson C, Palma A, Paredes N, Takeuchi O, Akira S, Julius M
Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Centre, The Toronto Hospital, Toronto, ON, Canada M5G 2M9.
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):603-8. doi: 10.1073/pnas.98.2.603.
Induction of resting B cell growth and differentiation requires a complex series of temporally coordinated signals that are initiated on contact with activated helper T cells. These signals complement one another, each rendering the B cell susceptible to factors supporting progressive activation. Here, we demonstrate that soluble CD14 (sCD14) bypasses the physiological sequelae of events that limit B cell activation. B cell growth and differentiation in vitro is induced by both native and recombinant forms of sCD14 at nanomolar concentrations. sCD14-mediated cellular activation does not require membrane CD14 expression, depends on a region of CD14 that is not involved in lipopolysaccharide binding, and requires functional Toll-like receptor 4. Consistent with biological activity of sCD14 in vitro, its administration to neonatal mice enhances Ig secretion. The results presented establish sCD14 as a naturally occurring soluble B cell mitogen of mammalian origin.
静止B细胞生长和分化的诱导需要一系列复杂的、在时间上协调的信号，这些信号在与活化的辅助性T细胞接触时启动。这些信号相互补充，每个信号都使B细胞对支持渐进性活化的因子敏感。在这里，我们证明可溶性CD14（sCD14）绕过了限制B细胞活化的生理事件后遗症。体外B细胞的生长和分化可由纳摩尔浓度的天然和重组形式的sCD14诱导。sCD14介导的细胞活化不需要膜CD14表达，依赖于CD14中不参与脂多糖结合的区域，并且需要功能性Toll样受体4。与sCD14在体外的生物学活性一致，将其给予新生小鼠可增强Ig分泌。所呈现的结果确立了sCD14作为一种天然存在的、源自哺乳动物的可溶性B细胞有丝分裂原。
