Hapten-induced B cell paralysis. II. Evidence for trivial mechanisms of tolerance.
Injection into mice of a free reactive form of the hapten (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP), induces a state of specific unresponsiveness to the hapten, upon its challenge with thymus-cependent and independent carriers. This unresponsiveness is maintained in vitro. Both induction and expression of the unresponsive state were found to be independent of T cells. Analysis of the mechanisms responsible for the B cell "tolerance" demonstrated that the major cause of unresponsiveness in this system is the blockade of specific surface receptors on B cells by the hapten, abolishing the focusing function of these receptors. "Tolerant" B cells, though they were unresponsive to the antigen, could be activated to anti-hapten antibody secretion by the B cell mitogen lipopolysaccharide (LPS), which does not require Ig-mediated binding. They also became fully responsive to the antigen NNP-LPS in specific thymus-independent responses after 24 hours of in vitro incubation in the absence of tolerogen, conditions which allow "deblocking" of Ig surface receptors, and, thus, restoration of the focusing function of these receptors. These results demonstrate that great care is required for a clearcut definition of B cell tolerance. In this example, the tolerant B cells were perfectly responsive to a competent ligand, and no indication of an altered triggering or effector processes was found. It appears that in this, as in many other cases of B cell tolerance, the systems or the animals are tolerant, whereas B cells maintain a resting nonactivated state and are fully responsive to the triggering signal. Thus, the existence of tolerance-inducing signals resulting in B cell unresponsiveness is questioned.
D000917:Antibody Formation; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001665:Binding Sites; D002462:Cell Membrane / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D004140:Dinitrophenols / Q000276:immunology / Q000494:pharmacology; D006241:Haptens; D007108:Immune Tolerance; D008070:Lipopolysaccharides / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
D004140:Dinitrophenols; D006241:Haptens; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D011947:Receptors, Antigen, B-Cell