Abstract: |
In-frame rearrangement of the TCR-β locus and expression of the pre-TCR are compulsory for the production of CD4+8+ thymocytes from CD4-8- precursors. Signals delivered via the pre-TCR are thought to induce the differentiation process as well as the extensive proliferation that accompanies this transition. However, it is equally possible that pre-TCR expression is required for the success of this transition, but does not play a direct role in the inductive process. In the present manuscript we examine this possibility using a variety of normal and genetically modified mouse models. Our evidence shows that differentiation and mitogenesis can both occur independently of pre-TCR expression. However, these processes are absolutely dependent on the presence of normal thymic architecture and cellular composition. These findings are consistent with a checkpoint role for the pre-TCR in regulating the divergence of survival and cell death fates at the CD4-8- to CD4+8+ transition. Further, our data suggest that precursor thymocyte differentiation is induced by other, probably ubiquitous, mechanisms that require the presence of normal thymic cellularity, composition, and architecture. |
Keywords: |
signal transduction; nonhuman; flow cytometry; cell proliferation; mitosis; animal cell; mouse; animal; mice; mice, knockout; cell death; cell survival; cell division; cell differentiation; mice, inbred c57bl; gene expression regulation; t lymphocyte receptor; lymphocyte activation; gene rearrangement; genes, t-cell receptor beta; thymus gland; stem cells; t-lymphocyte subsets; thymocyte; cell selection; receptors, antigen, t-cell, alpha-beta; cell composition; cytoarchitecture; dna content; priority journal; article; precursor cell; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; gene rearrangement, beta-chain t-cell antigen receptor
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