Kouro T, Medina K L, Oritani K, Kincade P W
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Blood. 2001 May 1;97(9):2708-15. doi: 10.1182/blood.v97.9.2708.
Recently, a collection of surface markers was exploited to isolate viable Lin(-) TdT(+) cells from murine bone marrow. These early pro-B cells were enriched for B-lineage lymphocyte precursor activity measured by short-term culture and had little responsiveness to myeloid growth factors. Early precursors can be propagated with remarkably high cloning frequencies in stromal cell-free, serum-free cultures, permitting this analysis of direct regulatory factors. Expression of the interleukin-7 receptor (IL-7Ralpha) chain marks functional precursors and IL-7 is necessary for progression beyond the CD45RA(+) CD19(-) stage. Efficient survival and differentiation were only observed when stem cell factor and Flt-3 ligand were also present. IL-7-responsive CD19(+) precursors are estrogen resistant. However, B-lineage differentiation was selectively abrogated when highly purified Lin(-) precursors were treated with hormone in the absence of stromal cells. In addition, early stages of B lymphopoiesis were arrested by limitin, a new interferon (IFN)-like cytokine as well as IFN-alpha, IFN-gamma, or transforming growth factor beta (TGF-beta), but not by epidermal growth factor (EGF). Lin(-) TdT(+) early pro-B cells are shown here to be CD27(+) AA4.1(+/-)Ki-67(+) Ly-6C(-) Ly-6A/Sca-1(Lo/-)Thy-1(-)CD43(+) CD4(+/-)CD16/32(Lo/-)CD44(Hi) and similar in some respects to the "common lymphoid progenitors" (CLP) identified by others. Although early pro-B cells have lost myeloid differentiation potential, transplantation experiments described here reveal that at least some can generate T lymphocytes. Of particular importance is the demonstration that a pivotal early stage of lymphopoiesis is directly sensitive to negative regulation by hormones and cytokines.
最近，人们利用一组表面标志物从鼠骨髓中分离出有活力的Lin(-)TdT(+)细胞。通过短期培养测定，这些早期前B细胞富含B淋巴细胞前体活性，对髓系生长因子反应较弱。早期前体在无基质细胞、无血清培养中能以极高的克隆频率增殖，从而可以对直接调控因子进行此分析。白细胞介素-7受体（IL-7Rα）链的表达标志着功能性前体，而IL-7是细胞超越CD45RA(+)CD19(-)阶段所必需的。只有当干细胞因子和Flt-3配体也存在时，才能观察到有效的存活和分化。IL-7反应性CD19(+)前体对雌激素有抗性。然而，当在无基质细胞的情况下用激素处理高度纯化的Lin(-)前体时，B淋巴细胞分化被选择性地消除。此外，B淋巴细胞生成的早期阶段会被一种新的干扰素（IFN）样细胞因子即极限素以及IFN-α、IFN-γ或转化生长因子β（TGF-β）阻断，但不会被表皮生长因子（EGF）阻断。此处显示Lin(-)TdT(+)早期前B细胞为CD27(+)AA4.1(+/-)Ki-67(+)Ly-6C(-)Ly-6A/Sca-1(Lo/-)Thy-1(-)CD43(+)CD4(+/-)CD16/32(Lo/-)CD44(Hi)，在某些方面与其他人鉴定的“常见淋巴祖细胞”（CLP）相似。尽管早期前B细胞已丧失髓系分化潜能，但此处描述的移植实验表明，至少一些早期前B细胞能够产生T淋巴细胞。特别重要的是证明了淋巴细胞生成的一个关键早期阶段对激素和细胞因子的负调控直接敏感。
