Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.

Abstract

In recent years it has become apparent that a variety of distinct mechanisms can lead to a state of specific immunologic tolerance. Clonal deletion of T and/or B lymphocytes (1), activation of specific suppressor T lymphocytes (2), and the production of small amounts of high affinity antibody (3) are among the well-defined mechanisms of immunologic unresponsiveness. At least two types of B-lymphocyte tolerance (reversible and irreversible) plus peripheral neutralization of antibody Ctreadmill hypothesis") have been definitively shown to operate in tolerance to T-independent antigens (4). In addition, recent studies have suggested that the interaction of antigen with antibodyproducing B lymphocytes can lead to a decrease in the rate of antibody secretion (effector cell blockade) (5) and that anti-idiotype antibody might be capable of mediating tolerance (6). Other than the observations of Weigle et al. (1) that higher doses of antigen are required for tolerance induction in B lymphocytes than in T lymphocytes, relatively little is known as to what factors determine which mechanism will be operative in any given unresponsive state.

Ontogeny of B-lymphocyte function. III. In vivo and in vitro studies on the ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice

“…Thus, it appears reasonable to regard this tolerant state as being mediated by a B-cell clonal deletion type mechanism. In previous studies (11) we established, by extensive cell transfer experiments, that the tolerant state induced in reconstituted irradiated adult mice with DNP-BGG is definitely due to a B-cell clonal deletion type mechanism. DNP-D-GL has been studied in detail and is known to be a B-cell tolerogen (20).…”

“…Studies were carried out as previously described in detail (10,11), by using lethally irradiated (800 R, from a gamma cell 40; Atomic Energy of Canada, Ltd.) thymectomized mice reconstituted with syngeneic lymphocytes. The source of fetal or neonatal B lymphocytes was the liver and the source of adult B cells was the spleen.…”

“…The target cells to detect anti-BGG PFC were prepared as described by Golub et al (14) by coupling 24 mg BGG to 0.5 ml washed, packed SRBC in phosphate-buffered saline, pH 6.0, by using 250 mg 1-ethyl-3 (3-dimethylaminopropyl)-carbodiimide HC1 (Sigma Chemical Co.). Anti-DNP PFC were detected by use of picryl coated SRBC as described previously (10,11,15).…”

“…3-13 days later all animals received 1 × l0 s syngeneic adult thymus cells, pooled from several adult donors. The anti-brain 0 antiserum was prepared by immunizing rabbits with CBA/J mouse brain in CFA as described and characterized previously (11).…”