Journal of Experimental Medicine, Vol 141, 974-989, Copyright © 1975 by Rockefeller University Press
Tolerance induction in B lymphocytes but thymus-dependent antigens. T cells may abrogate B-cell tolerance induction by prevent an antibody response
JW Schrader
Thymus-dependent protein antigens such as fowl gamma globulin (FGG) and
dinitrophenylated-human gamma globulin (DNP-HGG), readily induced tolerance
of the B cell in the absence of T cells even when these antigens were not
deaggregated. However, when the same doses of antigen were given in the
presence of T cells, the B-cell population was shown to be protected from
tolerance induction, especially when the antigen was not in a deaggregated
form. In this case, there was in fact evidence of a priming effect,
manifest in both the B-cell and T-cell populations. The priming effect on
the B-cell population was demonstrated by an increased response of mice
pretreated with DNP-HGG, upon challenge with DNP conjugated to a
heterologous carrier. The priming effect on the T-cell population was
evident in a helper effect demonstrated in vitro. However, when euthymic
mice which had been pretreated with large doses of FGG or DNP-HGG were
challenged with the homologous carrier, the results were different. In this
case, there was a profound suppression of the response against the carrier
or the hapten on that carrier. Suppressor activity was also demonstrated in
vitro and was shown to be sensitive to treatment with anti-theta-serum plus
complement. Additionally it was shown that the effector phase of the
suppression had a definite nonantigen-specific component. Thus, in
pretreated euthymic mice, provided the homologous carrier was present, the
response to a heterologous carrier was also suppressed. To account for the
observation that nondeaggregated antigens can induce B-cell tolerance in
athymic mice, but B-cell priming and T-cell-mediated suppression in
euthymic mice, it is proposed that B-cell tolerance occurs when antigen at
some critical dose interacts with the B cell in the absence of some second
signal. This second signal is normally provided by the macrophage, probably
with the assistance of the T cell, and its effect is to divert the result
of the interaction of the B cell with antigen towards immunization and away
from tolerance induction. When a large dose of an antigen that tends to
form aggregates is given to an animal possessing functional T cells, both
T-dependent helper and T-dependent suppressor activities are generated,
thus accounting for a situation where the B-cell population is immunized,
but B-cell activation is suppressed in the presence of the original
carrier.
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