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TCR beta-independent development of CD4+ CD8+ thymocytes observed in a strain of scid mice
1Department of Veterinary Science, National Institute of Health, Tokyo, Japan.
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.
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.