Palacios R, Stuber S, Rolink A
Basel Institute for Immunology, Switzerland.
Eur J Immunol. 1989 Feb;19(2):347-56. doi: 10.1002/eji.1830190220.
The Ly-1+ Mac-1+ B-220+ CC11+ progenitor clones LyD9 and LyB9 were previously shown to give rise to Ly-1+IgM+ B lymphocytes either in vivo or in vitro by co-culture with nonlymphoid accessory cells from spleen and lipopolysaccharide. The clones did not generate T lymphocytes either in vivo or in vitro. We now find that both LyD9 and LyB9 progenitors are induced to differentiate in vitro by co-culture with the RP.0.10 bone marrow stroma clone or with heterogeneous marrow-adherent stroma cell populations obtained from adult mice into Ly-1-IgM+ B lymphocytes as well as myeloid GM1.2+ Mac-1+ cells. We could obtain evidence that a high proportion of LyD9 and LyB9 cells already switched off expression of Ly-1 and CC11 (interleukin 3 receptor) surface molecules 2 days after initiation of the cultures, and by days 8-10 of culture no detectable Ly-1+ cells and only about 20% CC11+ cells were observed. Ly-1 surface expression could not be re-induced on the progeny of LyD9 and LyB9 progenitors generated under the influence of marrow stroma cells. Remarkably, the LyD9 and LyB9 progenitors gave rise to both Ly-1+IgM+ and Ly-1-IgM+ B cells upon culture with heterogeneous stroma monolayers obtained from 18-day fetal liver. Finally, the differentiating property of the stroma cells for the LyD9 and LyB9 progenitors could not be replaced with soluble factors produced either spontaneously or after stimulation by the marrow stroma cells. Our results show the importance of epigenetic influences provided by a given microenvironment on the developmental potential of B cell progenitors. They provide direct evidence that the same pro-B lymphocyte can give rise to both Ly-1+ and Ly-1-IgM+ B cells depending on both the time of development and the tissue of origin of stroma cells with which the B cell progenitor interacts. Also, the results strongly suggest that cell contact between the stroma cell and the B cell progenitor is essential to induce rearrangement and expression of the Ig genes in pro-B lymphocytes.
先前的研究表明，Ly-1⁺Mac-1⁺B-220⁺CC11⁺祖细胞克隆LyD9和LyB9，通过与来自脾脏的非淋巴细胞辅助细胞和脂多糖进行共培养，在体内或体外均可产生Ly-1⁺IgM⁺B淋巴细胞。这些克隆在体内或体外均不产生T淋巴细胞。我们现在发现，通过与RP.0.10骨髓基质克隆或从成年小鼠获得的异质性骨髓黏附基质细胞群体进行共培养，LyD9和LyB9祖细胞在体外均被诱导分化为Ly-1⁻IgM⁺B淋巴细胞以及髓系GM1.2⁺Mac-1⁺细胞。我们能够获得证据表明，在培养开始2天后，高比例的LyD9和LyB9细胞已经关闭了Ly-1和CC11（白细胞介素3受体）表面分子的表达，并且在培养的第8至10天，未观察到可检测到的Ly-1⁺细胞，仅观察到约20%的CC11⁺细胞。在骨髓基质细胞影响下产生的LyD9和LyB9祖细胞的后代上，Ly-1表面表达无法被重新诱导。值得注意的是，当与从18天龄胎儿肝脏获得的异质性基质单层进行培养时，LyD9和LyB9祖细胞可产生Ly-1⁺IgM⁺和Ly-1⁻IgM⁺B细胞。最后，基质细胞对LyD9和LyB9祖细胞的分化特性，不能被骨髓基质细胞自发产生或刺激后产生的可溶性因子所替代。我们的结果显示了特定微环境提供的表观遗传影响对B细胞祖细胞发育潜能的重要性。它们提供了直接证据，表明同一个前B淋巴细胞可根据发育时间以及与B细胞祖细胞相互作用的基质细胞的起源组织，产生Ly-1⁺和Ly-1⁻IgM⁺B细胞。此外，结果强烈表明，基质细胞与B细胞祖细胞之间的细胞接触对于诱导前B淋巴细胞中Ig基因的重排和表达至关重要。
