Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen.
Transgenic (Tg) mice expressing a foreign Ag, hen egg lysozyme (HEL), under control of the alphaA-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 of T 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.
de Vos
A F
AF
National Eye Institute and National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fukushima
A
A
Lobanoff
M C
MC
Vistica
B P
BP
Lai
J C
JC
Grivel
J C
JC
Wawrousek
E F
EF
Whitcup
S M
SM
Gery
I
I
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007908:Lens, Crystalline / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000235:genetics; D017634:Self Tolerance / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D000954:Antigens, Surface; D001324:Autoantigens; D016207:Cytokines; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D009113:Muramidase