Studies on hapten-specific B cell tolerance in vitro. II. Regulation of central tolerance in T-independent B cells by antigen-activated syngeneic T cells
Chen, S.; Cerny, J.
Journal of Immunology 125(5): 1970-1976
1980
ISSN/ISBN: 0022-1767 PMID: 6776185 Document Number: 163932
Specific central tolerance to trinitrophenol (TNP)-Ficoll, a T-independent antigen (TID) was induced in B cells by a 2 h pulse with TNP-keyhole limpet hemocyanin (TNP16-KLH, 50 .mu.g/107 lymphocytes), followed by washing and an 18 h culture in antigen-free media. B cells were obtained as spleen cells from thymectomized, irradiated, bone marrow-reconstituted mice or from normal spleen cells by repeated treatment with anti-.theta. antibody plus complement (C). Lymphocytes from virgin and hapten-primed (TNP-tetanus toxoid-immunized) mice were readily tolerized; cells from mice immunized with KLH were relatively resistant to tolerance induction with TNP-KLH. The induction of tolerance in virgin and hapten-primed B cells was prevented (reversed) by addition of small numbers of KLH-primed spleen cells unless the latter were pretreated with anti-.theta. antibody + C. The KLH-primed T cells were capable of reversing the tolerance when added with the TNP-KLH tolerogen and when added at 18 h after the tolerance induction. The effect was not specific for the tolerogen carrier protein since T cells from KLH-primed mice reversed the induction of tolerance by TNP coupled to bovine .gamma.-globulin (TNP33-BGG), provided that free KLH was present in the media during the pulse with the tolerogen. The TNP-specific tolerance was induced in B cells responsive to TNP-Ficoll (a TID-2 antigen) and to TNP-Brucella abortus (TNP-BA) (a TID-1 antigen), although the response to TNP-BA was less suppressed (by .simeq. 70%) than that to TNP-Ficoll (.gtoreq. 90% suppression). A reversal of tolerance to TNP-BA required .apprx. 10 times more carrier-primed T cells than reversal of the TNP-Ficoll tolerance. Antigen-activated T cells may abrogate the induction of central tolerance in TID subsets of B cells (that require little or no help for triggering). The mechanism of tolerance reversal may differ from the classical helper effect, it does not require antigen bridging between the B and T cell.