Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice.
Mice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273-280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR alpha and beta chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B-I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.|Present addresses: Weatherall Institute for Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, GB; M. F. Lopes, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janiero, Brazil.
Adrian A
AA
Lobito
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.
Marcela F
MF
Lopes
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.
Michael J
MJ
Lenardo
D000818:Animals; D000917:Antibody Formation; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002452:Cell Count; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015870:Gene Expression; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
D016693:Receptors, Antigen, T-Cell, alpha-beta