3 results
Search Results
2. Equivalence of conventional anti-picryl T suppressor factor in the contact sensitivity system and monoclonal anti-NP TsF3: their final non-specific effect via the T acceptor cell.
- Author
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Asherson, G. L., Dorf, M. E., Colizzi, V., Zembala, M., and James, Bridget M. B.
- Subjects
- *
ANTIGENS , *SUPPRESSOR cells , *HYBRIDOMAS , *SPLEEN , *THYMECTOMY , *LABORATORY mice - Abstract
There is considerable confusion over whether the antigen-specific T suppressor factors (TsF) described by different authors are indeed equivalent. This paper investigates whether monoclonal TsF3, obtained from hybridomas derived from mice injected subcutaneously with NP derived spleen cells. is functionally equivalent to the conventional T suppresser factor, produced by mice injected intravenously with chemically reactive, water soluble haptene (picrylsulphonic acid and oxazolone thioglycolic acid). Comparison of monoclonal anti-NP TsF3 with conventional anti-picryl and anti-oxazolone T suppressor factor showed that both armed the non-specific T accepter cell (Tacc) which was sensitive to cyclophosphamide and adult thymectomy. Moreover, non-specific inhibitor (nsINH) of the transfer of contact sensitivity was released when antigen, together with major histocompatibility complex products (MHC). reacted with conventional or monoclonal TsF on the surface of the non-specific T accepter cell. The interaction of monoclonal TsF3 with antigen, which led to the release of nsINH, required the presence of MHC and was I-J restricted. However, there was no Igh-1 restriction. The equivalence of conventional anti-picryl and anti-oxazolone TsF has been demonstrated by arming the Tacc with a mixture of these two suppressor factors, and then triggering the release of nsINH with the mixed haptene ‘picryl-oxazolone-lysine’ which crosslinks separate molecules of TsF. A similar equivalence of conventional anti-oxazolone TsF and monoclonal anti-NP TsF3 was demonstrated using the mixed hapten ‘NP-oxazolone-lysine’ to trigger the release of nsINH. It was concluded that monoclonal TsF3 and conventional TsF were equivalent, and that both had an indirect mode of action through the non-specific T acceptor cell which led to the production of non-specific inhibitor. [ABSTRACT FROM AUTHOR]
- Published
- 1984
3. Mechanisms of clonal abortion tolerogenesis II. CLONAL BEHAVIOUR OF IMMATURE B CELLS FOLLOWING EXPOSURE TO ANTI-μ CHAIN ANTIBODY.
- Author
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Nossal, G. J. V., Pike, Beverley L., and Battye, F. L.
- Subjects
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B cells , *IMMUNOGLOBULINS , *LYMPHOCYTES , *CLONING , *LABORATORY mice , *SPLEEN - Abstract
This paper uses B-lymphocyte cloning methods to quantify the effects of anti-μ chain antibody on immature and mature B cells. Nude mouse spleen lymphocytes were incubated with various concentrations of sheep anti-mouse μ chain antibody for times varying from 10 min to 24 h. They were then washed and plated in the agar B-cell colony formation assay. Five to six days later, control B cells had developed into colonies with a plating efficiency of about 5%. B cells from newborn mice pretreated with anti-μ yielded fewer colonies. Remarkably low concentrations sufficed to inhibit subsequent mitogenesis. For example, 3 μg/ml acting for 1 h or 0.1 μg/ml acting for 24 h gave > 50% inhibition. Adult B cells were about thirty-fold more resistant to negative signalling. Immature cells became more profoundly inhibited as anti-μ treatment was prolonged. Anti-Ia or anti-H2 antibodies, in the absence of complement, did not deliver a negative signal. Anti-μ pretreatment also reduced the capacity of immature B cells to form clones of anti-hapten antibody-forming cells in a liquid microculture system where the triggering stimulus was a T-cell independent antigen. Mature 'T-independent' B cells were not inhibited. Populations of hapten-specific B cells prepared by the hapten-gelatin method were investigated in the agar cloning system. Pretreatment of immature cells with anti-μ reduced their capacity to form colonies, this subpopulation of cells behaving like unfractionated B cells. Furthermore, hapten--HGG delivered a negative signal also. Mature hapten-specific cells or unfractionated immature spleen cells formed normal numbers of colonies following hapten HGG treatment. Overall, the studies support the view that anti-μ antibody and hapten--HGG deliver strong negative signals to immature but not mature cells with appropriate receptors. The value of anti-μ as a model, universal tolerogen was supported. Fluorescence-activated cell sorter (FACS) analysis was performed to study the relationships between functional inhibition and Ig receptor modulation. We confirmed that the IgM receptors of immature B cells are more readily modulated by anti-μ antibody than those of mature cells. Furthermore, the receptor regeneration could be partially inhibited amongst immature but not mature B cells. There was not a close quantitative relationship between the degree of modulation and the degree of functional inhibition. The results did not support the view that irreversible receptor modulation as such was the cause of functional inhibition. [ABSTRACT FROM AUTHOR]
- Published
- 1979
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