Shibata S, Asano T, Ogura A, Hashimoto N, Hayakawa J, Naiki M, Doi K
Department of Veterinary Science, National Institute of Health, Tokyo, Japan.
Immunol Cell Biol. 1997 Apr;75(2):154-60. doi: 10.1038/icb.1997.21.
Mice homozygous for severe combined immunodeficiency (scid) mutation usually halt their thymocyte development at the CD4-CD8- double negative (DN) stage due to their inability of TCR gene rearrangement. In this study, we report that SCID-bg mice, which were originally generated by mating CB-17-scid mice with KSN-bg mice, spontaneously develop dominant CD4+ CD8+ double positive (DP) thymocytes. Their thymi were mainly composed of DN, CD4-CD8+ and DP cells, and the majority of them did not present CD3. Similarly, they lacked TCR beta expression both on cell surface and in cytoplasm, which suggests that the thymocyte development to the DP stage observed in SCID-bg mice, was independent of CD3 and TCR beta expression. In spite of significant DP thymocytes in SCID-bg mice, the histology of their thymi was not so different from those of CB-17-scid mice. Analysis of bone marrow cells in SCID-bg mice showed that the development of B lineage cells was not altered when compared with CB-17-scid mice. These findings point out the fact that thymocytes in SCID-bg mice have a peculiar characteristic compared to CB-17-scid mice, and provide evidence of TCR beta-independent development of thymocytes to the DP stage.
由于TCR基因重排功能缺失,纯合严重联合免疫缺陷(scid)突变的小鼠通常在CD4-CD8-双阴性(DN)阶段停止胸腺细胞发育。在本研究中,我们报告称,最初通过将CB-17-scid小鼠与KSN-bg小鼠交配产生的SCID-bg小鼠会自发产生占主导地位的CD4+CD8+双阳性(DP)胸腺细胞。它们的胸腺主要由DN、CD4-CD8+和DP细胞组成,且大多数细胞不表达CD3。同样,它们在细胞表面和细胞质中均缺乏TCRβ表达,这表明在SCID-bg小鼠中观察到的胸腺细胞发育至DP阶段与CD3和TCRβ表达无关。尽管SCID-bg小鼠中有大量DP胸腺细胞,但其胸腺的组织学与CB-17-scid小鼠的胸腺并无太大差异。对SCID-bg小鼠骨髓细胞的分析表明,与CB-17-scid小鼠相比,B淋巴细胞系的发育没有改变。这些发现指出了一个事实,即与CB-17-scid小鼠相比,SCID-bg小鼠的胸腺细胞具有独特的特征,并为胸腺细胞在不依赖TCRβ的情况下发育至DP阶段提供了证据。