Intrathymic presentation of nominal antigen by B cells

Abstract

Prenatal tolerization with TNBS leads to a transient increase in intrathymic TNP-specific B cells during the first postnatal week. To evaluate whether this may influence selection of the T cell repertoire and establishment of tolerance towards the neoself-determinant TNP, the capacity of intrathymic B cells to present TNP as well as an anti-TNP antibody (Sp6), which carries a recurrent idiotype, to thymocytes of prenatally untreated and TNBS-treated litters was explored. Depletion and reconstitution experiments revealed that in the thymus of 10-day-old litters Sp6 as well as TNP was presented exclusively by B cells. After stimulation with TNP-HRBC, B cells could still present the antigen, but depletion of B cells no longer abolished proliferation, i.e. after stimulation intrathymic B cells were no longer the only source for presentation of external antigen. B cells of prenatally tolerized mice differed inasmuch as they initiated proliferation only in response to Sp6, but not in response to the neoself-determinant TNP. Furthermore, after challenge with TNP in an immunogenic form, thymic as well as splenic B cells had lost the capacity to provide positive signals to T cells specific for the neoself determinant as well as to T cells specific for the cognate antibody. It is concluded that B cells are of importance in the intrathymic selection of the T cell repertoire and that they are involved in the process of tolerization towards nominal antigen.