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Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice
Adrian A Lobito1,2, Marcela F Lopes1, Michael J Lenardo1
1Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.
European Journal of Immunology
|March 3, 2004
Summary
Transgenic T cell receptor (TCR) expression in mice caused B cell immunodeficiency. This occurred due to TCR chains accumulating in B cells, triggering endoplasmic reticulum stress and apoptosis, revealing a novel immunodeficiency mechanism.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Transgenic T cell receptors (TCRs) are crucial tools for studying immunity.
- Previous work identified a B cell immunodeficiency in mice with a transgenic TCR specific for the nicotinic acetylcholine receptor.
Purpose of the Study:
- To elucidate the mechanism behind the B cell immunodeficiency observed in transgenic TCR mice.
- To investigate the impact of inappropriate transgene expression on B cell development and function.
Main Methods:
- Analysis of B cell populations in transgenic mice.
- Investigation of TCR alpha and beta chain expression within B cells.
- Assessment of endoplasmic reticulum (ER) stress markers and apoptosis induction in B cells.
Main Results:
- TCR alpha and beta chains were found to be expressed and accumulated within B cells.
- This accumulation induced a significant endoplasmic reticulum stress response.
- Apoptosis was observed in pre-B-I and later stage B cells, correlating with ER stress.
Conclusions:
- Inappropriate expression of transgenic TCRs can lead to B cell immunodeficiency.
- Accumulation of TCR chains in B cells triggers ER stress and apoptosis, a novel mechanism of immune dysfunction.
- This highlights the importance of considering transgene expression effects on non-target cell types.