Cells of immunoglobulin synthesis / edited by Benvenuto Pernis, Henry J. Vogel.

Date:
1979
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Cells of immunoglobulin synthesis / edited by Benvenuto Pernis, Henry J. Vogel. Source: Wellcome Collection.

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    в LYMPHOCYTE DIFFERENTIATION AND THE TOLERANCE PROBLEM 5 The special susceptibility of adult marrow small lymphocytes to toler¬ ance induction has also been documented (2), but we have not yet pursued this among marrow cells sorted on the basis of their Ig density. KINETICS OF TOLEROGENESIS AMONG IMMATURE В CELLS OF VARIOUS CATEGORIES In support of the clonal abortion theory of В lymphocyte tolerance (4) we have previously drawn attention to the fact that fetal liver stem cells repopulating irradiated mice (10), adult bone marrow cells (4) and newborn spleen cells (11,2) all can be rendered tolerant by sur¬ prisingly low concentrations of antigen. However, in our previous work, tolerance induction among the hapten-specific В cells under study involved a prolonged period of co-incubation of the cell popula¬ tion with tolerogenic antigen. In fact, maximal effects were seen only when tolerogen and the cell population were held together for 3 days. Over such a period, control populations not being tolerized matured considerably, increasing their capacity to give adoptive immune re¬ sponses or to initiate clones of antibody-forming cells in vitro. The chief efiFect of the tolerogen was to abrogate this maturation in a hapten-specific manner. For this reason, the studies did not produce evidence for a direct efiFect of tolerogen on the few triggerable cells present in the immature cell population at the beginning of the culture period. The existence of immature В cells, capable of being activated to clonal expansion and antibody formation through the action of antigen plus T cell help, yet capable of being rendered tolerant by very low concentrations of antigen in the absence of T cell activity, was shown by the work of Klinman's group (12,13). Their studies on the toleriza- bility of the immature В cell paralleled ours in several respects, but one important difiference was noted. The degree of tolerance reached within 8 hr was near maximal. Clearly, the negative signal was being read by a cell that could also respond to a positive signal, not simply by the progenitor of the triggerable cell. To solve this apparent difiference in results and interpretation, we decided to attempt to isolate the immature В cell capable of behaving in this dual fashion in relatively pure form. D. W. Scott, at that time part of our group, termed these the caught in the act of clonal abor¬ tion experiments. If Ig-negative cells could be eliminated from con¬ sideration, there would be no contribution from pre-B cells. Further-
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