Identification of CD19-B220+c-Kit+Flt3/Flk2+ cells as early B lymphoid precursors before pre-B-I cells in juvenile mouse bone marrow
Identification of CD19-B220+c-Kit+Flt3/Flk2+ cells as early B lymphoid precursors before pre-B-I cells in juvenile mouse bone marrow
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DOI：
10.1093/intimm/12.3.313
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发表时间：
2000-03-01
影响因子：
4.4
通讯作者：
Melchers, F
中科院分区：
文献类型：
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作者：
Ogawa, M;ten Boekel, E;Melchers, F
通过对1周龄小鼠骨髓中受体酪氨酸激酶c-Kit和Flt3/Flk-2的表达以及人CD25基因在小鼠lambda 5启动子调控下的转基因表达的联合分析，我们可以识别CD19(+)c-Kit(+)Pre-B-I细胞之前B淋巴细胞发育的三个阶段。对免疫球蛋白重链等位基因重排状态的单细胞PCR分析使我们能够对B细胞发育的这些早期阶段进行如下排序：(I)B220(+)CD19(-)c-Kit(Lo)Flt3/Flk-2(Hi)lambda 5(-)，(Ii)B220(+)CD19(-)c-Kit(Lo)Flt3/Flk-2(Hi)lambda 5(+)和(Iii)B220(+)CD19(+)c-Kit(Lo)lambda 5(+)在B220(+)CD19(+)c-Kit(Lo)Flt3/Flk2-lambda 5(+)Pre-B-I细胞之前。在IL-7存在下，这些祖细胞均可在基质细胞上克隆，并可分化为CD19(+)c-Kit(-)B系细胞。在悬浮培养中，干细胞因子、Flt3配体和IL-7的组合也能够支持祖细胞的增殖和分化。此外，分析表明，D(H)J(H)重排的开始先于lambda 5基因的表达。这些祖细胞群是幼年鼠的特征，在成年鼠的骨髓中检测不到。因此，在幼年和成年小鼠中，受体酪氨酸激酶在B细胞分化早期的表达模式和可能的功能似乎是不同的。
The combined analysis of the expression of receptor tyrosine kinases c-Kit and Flt3/Flk-2 and of the human CD25 gene expressed as a transgene under the regulation of the mouse lambda 5 promoter in the bone marrow of 1-week-old mice allows us to identify three stages of B lymphocyte development before the CD19(+)c-Kit(+) pre-B-I cells. Single-cell PCR analysis of the rearrangement status of the Ig heavy chain alleles allows us to order these early stages of B cell development as follows: (i) B220(+)CD19(-)c-Kit(lo)Flt3/Flk-2(hi)lambda 5(-), (ii) B220(+)CD19(-)c-Kit(lo)Flt3/Flk-2(hi)lambda 5(+) and (iii) B220(+)CD19(+)c-Kit(lo)Flt3/Flk-2(lo)lambda 5(+) before B220(+)CD19(+)c-Kit(lo)Flt3/Flk2-lambda 5(+) pre-B-I cells. All these progenitors are clonable on stromal cells in the presence of IL-7 and can differentiate to CD19(+) c-Kit(-) B-lineage cells. A combination of stem cell factor, Flt3 ligand and IL-7 was also able to support the proliferation and differentiation of the progenitors in a suspension culture. Furthermore, the analyses indicate that the onset of D(H)J(H) rearrangements precedes the expression of the lambda 5 gene. These progenitor populations were characteristic of juvenile mice and could not be detected in the bone marrow of adult mice. Hence the expression pattern, and probably the function, of the receptor tyrosine kinases in early B cell differentiation appears to be different in juvenile and adult mice.