Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen

Alexander F. De Vos, Atsuki Fukushima, Mark C. Lobanoff, Barbara P. Vistica, James C. Lai, Jean Charles Grivel, Eric F. Wawrousek, Scott M. Whitcup, Igal Gery

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Abstract

Transgenic (Tg) mice expressing a foreign Ag, hen egg lysozyme (HEL), under control of the αA-crystallin promoter ('HEL-Tg' mice) develop immunotolerance to HEL attributed to the expression of HEL in their thymus. In this paper we analyzed the immune response in double (Dbl)-Tg mice generated by mating the HEL-Tg mice with Tg mice that express HEL Abs on their B cells ('Ig-Tg' mice). The B cell compartment of the Dbl-Tg mice was unaffected by the HEL presence and was essentially identical to that of the Ig-Tg mice. A partial breakdown of tolerance was seen in the T cell response to HEL of the Dbl-Tg mice, i.e., their lymphocyte proliferative response against HEL was remarkably higher than that of the HEL-Tg mice. T-lymphocytes of both Dbl-Tg and Ig-Tg mice responded to HEL at concentrations drastically lower than those found stimulatory to lymphocytes of the wild-type controls. Cell mixing experiments demonstrated that 1) the lymphocyte response against low concentrations of HEL is due to the exceedingly efficient Ag presenting capacity of the Ab expressing B cells and 2) breakdown of tolerance in Dbl-Tg mice can also be attributed to the APC capacity of B cells, that sensitize in vivo and stimulate in vitro populations oft cells with low affinity toward HEL, assumed to be escapees of thymic deletion. These results thus indicate that T cell tolerance can be partially overcome by the highly potent Ag presenting capacity of Ab expressing B cells.

Original languageEnglish
Pages (from-to)4594-4600
Number of pages7
JournalJournal of Immunology
Volume164
Issue number9
DOIs
Publication statusPublished - 1 May 2000

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

De Vos, A. F., Fukushima, A., Lobanoff, M. C., Vistica, B. P., Lai, J. C., Grivel, J. C., Wawrousek, E. F., Whitcup, S. M., & Gery, I. (2000). Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen. Journal of Immunology, 164(9), 4594-4600. https://doi.org/10.4049/jimmunol.164.9.4594