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*
National Eye Institute and
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20814
Transgenic (Tg) mice expressing a foreign Ag, hen egg lysozyme
(HEL), under control of the 
A-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.
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