Tolerance induction in resting memory B cells specific for a protein antigen.
Resting memory B lymphocytes specific for the model protein Ag cytochrome c have been shown to be susceptible to tolerance induction in in vitro splenic fragment cultures. This induction of nonresponsiveness is dependent upon the strength of the interaction between surface Ig and specific Ag, where concentration, valency, affinity, and time of exposure all appear to be important factors, as is the case for tolerance induction in immature or primary B cells. The induction of nonresponsivenes in greater than 80% of Ag-specific memory B cells was achieved by incubation with 1 microM cytochrome polymer for 24 h in the absence of T cell help. Not only were memory B cells unresponsive to specific Ag, they were also unable to become activated through nonspecific uptake and presentation of an Ag to which T cells have been primed, demonstrating that the induction of nonresponsiveness involves more than a modulation or blockade of surface Ig receptors. Although soluble factors collected from activated T cells failed to prevent memory B cells from becoming nonresponsive after surface Ig cross-linking, the direct activation of T cells within splenic fragment cultures did partially inhibit tolerance induction in splenic fragment memory B cells. In addition, the induction of tolerance was partially blocked by protein tyrosine kinase inhibitors, suggesting a physiologic change within the B cells associated with the state of nonresponsiveness and resulting from tyrosine-specific phosphorylation.
Johnson
J G
JG
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455.
Jemmerson
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016227:Benzoquinones; D002396:Catechols / Q000494:pharmacology; D003574:Cytochrome c Group / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019833:Genistein; D007136:Immunoglobulins / Q000502:physiology; D007165:Immunosuppression Therapy / Q000379:methods*; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D020032:Tyrphostins
D016227:Benzoquinones; D002396:Catechols; D003574:Cytochrome c Group; D007136:Immunoglobulins; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D009570:Nitriles; D011809:Quinones; D020032:Tyrphostins; C060152:tyrphostin 47; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases