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Coding joint formation of endogenous T cell receptor genes in lymphoid cells from scid mice: unusual P-nucleotide
W Schuler1, N R Ruetsch, M Amsler
1Basel Institute for Immunology, Switzerland.
Abstract:
The mouse mutation scid adversely affects the process of VDJ recombination. Attempts to form coding joints, that is, to joint V or D to J gene segments generally fail in developing scid lymphocytes. It has been proposed that the scid mutation results a defective VDJ recombinase system. Here we describe five scid T cell lymphomas containing one or two TcR gamma coding joints each, even though the majority of the multiple TcR gamma chain gene rearrangements and all TcR beta rearrangements in these cells were abnormal with the deletions typically found in scid lymphoid cells. One of the five T cell lymphomas was shown to have an active VDJ recombinase system; however, this activity was defective indicating that the scid phenotype has been retained. We conclude that the scid VDJ recombinase system has not completely lost the ability to form coding joints. P-nucleotide additions of unusual length or composition were found at the junctional border in five of the eight TcR gamma coding joints. This might reflect a defect in the activity of a component of the VDJ recombinase system involved in the generation of P-nucleotide additions. In one of the observed rearrangements, a V gamma 5-J gamma 3 coding joint was formed. This establishes the transcriptional orientation of J gamma 3-C gamma 3 and confirms a previously proposed organization of the TcR gamma genes.
Insights
The severe combined immunodeficiency (scid) mutation impairs VDJ recombination in lymphocytes. However, this study found that scid T cell lymphomas can still form some coding joints, indicating a partially retained VDJ recombinase activity.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- The severe combined immunodeficiency (scid) mutation in mice is known to disrupt VDJ recombination, a critical process for adaptive immune system development.
- This disruption typically leads to failed attempts to join V, D, and J gene segments in developing lymphocytes, suggesting a defective VDJ recombinase system.
Purpose of the Study:
- To investigate the VDJ recombination process in scid T cell lymphomas.
- To determine if the scid mutation completely abolishes the ability to form coding joints or if some residual activity exists.
Main Methods:
- Analysis of T cell lymphomas from scid mice.
- Examination of T cell receptor (TcR) gamma and beta gene rearrangements.
- Assessment of VDJ recombinase activity in scid T cell lymphomas.
Main Results:
- Five scid T cell lymphomas were found to contain one or two T cell receptor (TcR) gamma coding joints, despite abnormal TcR gamma and beta rearrangements.
- One lymphoma exhibited active but defective VDJ recombinase activity, confirming the retention of the scid phenotype.
- Unusual P-nucleotide additions were observed at the junctional borders of TcR gamma coding joints, suggesting a defect in their generation.
Conclusions:
- The scid VDJ recombinase system retains some ability to form coding joints, rather than being completely non-functional.
- A defect in the VDJ recombinase system component responsible for P-nucleotide additions may be present in scid lymphocytes.
- The formation of a specific V gamma 5-J gamma 3 coding joint confirmed the transcriptional orientation of J gamma 3-C gamma 3 and TcR gamma gene organization.