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 B. Grivel, Eric F. Wawrousek, Scott M. Whitcup, Igal Gery

Research output: Contribution to journalArticle

15 Citations (Scopus)

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
Publication statusPublished - 1 May 2000
Externally publishedYes

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Autoantigens
Transgenic Mice
B-Lymphocytes
Antigens
Lymphocytes
T-Lymphocytes
hen egg lysozyme
Crystallins
Thymus Gland

ASJC Scopus subject areas

  • Immunology

Cite this

De Vos, A. F., Fukushima, A., Lobanoff, M. C., Vistica, B. P., Lai, J. C., Grivel, J-C. B., ... 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.

Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen. / De Vos, Alexander F.; Fukushima, Atsuki; Lobanoff, Mark C.; Vistica, Barbara P.; Lai, James C.; Grivel, Jean-Charles B.; Wawrousek, Eric F.; Whitcup, Scott M.; Gery, Igal.

In: Journal of Immunology, Vol. 164, No. 9, 01.05.2000, p. 4594-4600.

Research output: Contribution to journalArticle

De Vos, AF, Fukushima, A, Lobanoff, MC, Vistica, BP, Lai, JC, Grivel, J-CB, Wawrousek, EF, Whitcup, SM & 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, vol. 164, no. 9, pp. 4594-4600.
De Vos AF, Fukushima A, Lobanoff MC, Vistica BP, Lai JC, Grivel J-CB et al. Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen. Journal of Immunology. 2000 May 1;164(9):4594-4600.
De Vos, Alexander F. ; Fukushima, Atsuki ; Lobanoff, Mark C. ; Vistica, Barbara P. ; Lai, James C. ; Grivel, Jean-Charles B. ; Wawrousek, Eric F. ; Whitcup, Scott M. ; Gery, Igal. / Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen. In: Journal of Immunology. 2000 ; Vol. 164, No. 9. pp. 4594-4600.
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