Bone marrow stromal cells and interleukin-7 induce coordinate expression of the BP-1/6C3 antigen and pre-B cell growth.

Bone marrow stromal cells and interleukin-7 induce coordinate expression of the BP-1/6C3 antigen and pre-B cell growth.
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DOI:
10.1093/intimm/2.8.697
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发表时间:
1990-08
影响因子:
4.4
通讯作者:
P. Welch;P. Burrows;A. Namen;S. Gillis;M. Cooper
P. Welch;P. Burrows;A. Namen;S. Gillis;M. Cooper
中科院分区:
医学3区
文献类型:
--
作者:
P. Welch;P. Burrows;A. Namen;S. Gillis;M. Cooper

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早期B系细胞和某些基质细胞表达的BP-1/6C3分子是一种II型完整膜糖蛋白,属于锌依赖金属肽酶家族。为了探讨这种细胞表面分子在前体B细胞增殖中的潜在作用,我们建立了一株长期培养的Whitlock-Witte型骨髓基质细胞系(BHM),并建立了一种快速检测反应靶细胞的生物测定方法。当未贴壁的骨髓细胞与骨髓基质一起培养时,我们观察到B细胞前体上调了BP-1的表达,这与诱导增殖是一致的。前体B细胞靶点包括缺乏可检测到的BP-1/6C3、B220和Ia抗原的骨髓细胞。在正常BALB/c小鼠的胎肝和骨髓中均可检测到它们的存在,但在胸腺、脾或淋巴结中未发现,在nu/nu、CBA/N和SCID缺陷小鼠的骨髓中也有表达。由于BHM培养上清液对前体B细胞的诱导作用可以复制,因此在实验中对可溶性生长因子进行了评估。白介素7(IL-7)在诱导BP-1/6C3表达和伴随细胞生长方面似乎是独一无二的。Northern印迹分析表明,BHM基质细胞本身表达BP-1抗原,并结构性地表达IL-7的高水平可变长度转录本。结果提示,基质细胞IL-7产物选择性地诱导B细胞前体细胞表达BP-1/6C3,并可能参与控制IL-7诱导的早期B细胞的增殖。
The BP-1/6C3 molecule expressed by early B lineage cells and some stromal cells is a type II integral membrane glycoprotein that belongs to the zinc-dependent family of metallopeptidases. In order to explore the potential role of this cell surface molecule in precursor B cell proliferation, we established a stromal cell line (BHM) from long-term bone marrow cultures of the Whitlock - Witte type and developed a rapid bioassay for the detection of responsive target cells. When non-adherent bone marrow cells were cultured with BHM stroma, we observed an up-regulation of BP-1 expression by the B cell precursors that coincided with the induction of proliferation. The precursor B-cell targets included bone marrow cells that lacked detectable BP-1/6C3, B220, and Ia antigens. They could be identified in fetal liver and in the bone marrow, but not the thymus, spleen, or lymph nodes, of normal BALB/c mice, and were also present in the bone marrow of mice with the nu/nu, CBA/N, and SCID defects. Because the inductive effects on precursor B cells could be reproduced with BHM supernatant, soluble growth factors were evaluated in the assay. Interleukin 7 (IL-7) appeared to be unique in its ability to induce BP-1/6C3 expression and concomitant cell growth. Northern blot analysis revealed that the BHM stromal cells, which themselves express the BP-1 antigen, constitutively expressed high levels of variable length transcripts for IL-7. The data suggest that the IL-7 product of stromal cells selectively induces BP-1/6C3 expression on B cell precursors and may implicate this cell surface glycoprotein in the control of IL-7 induced proliferation of early B lineage cells.