Resistance to lymphoid engraftment in lpr recipients of normal bone marrow: characterization of chimeric stem cell, monocyte and peripheral lymphoid lineages.
Resistance to lymphoid engraftment in lpr recipients of normal bone marrow: characterization of chimeric stem cell, monocyte and peripheral lymphoid lineages.
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正常骨髓 lpr 受体对淋巴移植的抵抗力：嵌合干细胞、单核细胞和外周淋巴谱系的特征。
DOI：
10.1002/eji.1830200908
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发表时间：
1990
影响因子：
5.4
通讯作者：
Marshak-Rothstein,A
中科院分区：
文献类型：
--
作者：
Glaser,RM;Marshak-Rothstein,A
经致命照射的MRL/ lpr小鼠用来自非自身免疫株a的T细胞耗尽的骨髓干细胞重组，其已被证明发展为长期分裂嵌合状态；红细胞来源于A. Thy供体，外周血淋巴细胞来源于受体。相比之下，非lpr同源菌株MRL/+的受体在两种谱系中都被供体来源的造血细胞完全重新填充。为了更充分地了解这种分裂嵌合的机制，我们研究了额外的遗传和发育参数。我们发现，组织相容性正常B细胞前体移植C3H/HeJ和C57BL/6/+小鼠的效果远好于移植相应的同源菌株，这表明对淋巴细胞移植的抗性并非MRL背景所独有。骨髓细胞和腹腔巨噬细胞在两种非受体中均表达供体H‐2表型，从而限制了对淋巴系的抵抗。此外，我们发现正常骨髓干细胞在无宿主环境中传代，随后能够重新填充非二级受体的B细胞谱系，证明前淋巴样干细胞是完整的。虽然A. Thy→MRL/ lpr嵌合体的淋巴结细胞是正常衍生的，但它们没有表现出与预表型相关的异常表面标记表达，也没有出现淋巴样增生或自身抗体水平升高。然而，A. Thy→MRL/ lpr嵌合体与正常小鼠不同的是，它们的脾脏中IgM+B细胞明显缺乏。
Lethally irradiated MRL/lprmice reconstituted with T cell‐depleted bone marrow stem cells from the non‐autoimmune strain A. Thy had been shown to develop a state of long‐term split chimerism; erythrocytes were derived from the A. Thy donor, while peripheral lymphocytes were derived from thelprrecipient. In contrast, recipients of the non‐lpr‐congenic strain, MRL/+, were fully repopulated in both lineages by donor‐derived hematopoietic cells. In order to more fully understand the mechanisms responsible for this type of split chimerism, we have investigated additional genetic and developmental parameters. We found that histocompatible normal B cell precursors engrafted C3H/HeJ and C57BL/6/+ mice much better than they engrafted the correspondinglprcongenic strains, indicating that resistance to lymphoid engraftment was not unique to the MRL background. Bone marrow cells and peritoneal macrophages were found to express the donor H‐2 phenotype in both non‐lprandlprrecipients, limiting resistance to the lymphoid lineage. Moreover, we showed that normal bone marrow stem cells passaged in anlprhost environment were subsequently able to repopulate the B cell lineage of non‐lprsecondary recipients, proving that prelymphoid stem cells were intact. Although lymph node cells from A. Thy → MRL/lprchimeras werelpr‐derived, they did not show the abnormal surface marker expression associated with thelprphenotype, nor did they develop lymphoid hyperplasia or elevated autoantibody levels. However, A. Thy → MRL/lprchimeras differed from normal mice in that their spleens were markedly deficient in IgM+B cells.