Idiotype shifts caused by neonatal tolerance to phosphorylcholine.
The injection of as little as 0.5 microgram phosphorylcholine-(PC) conjugated mouse immunoglobulin into BALB/c neonates within 48 hr of birth results in complete unresponsiveness to PC for 3 to 4 wk. Thereafter, anti-PC responses can be detected in tolerized animals, but these responses differ significantly from those of normal BALB/c mice. First, the magnitude of responsiveness does not approach normal levels even 9 mo after birth. Second, although the initial responses as tolerance is broken can be T15+, idiotypic dominance is not established; instead, a heterogeneous T15- population eventually emerges, which includes clones with higher and with lower avidity than T15. Unirradiated unresponsive mice will help transplanted normal B cells to produce T15+ responses to thymus-dependent PC antigens. The responses of animals recovered from tolerance are stable upon adoptive transfer. We have, moreover, found no evidence of either loss of idiotype-specific T cell help or generation of suppression. Therefore, neonatal exposure to PC tolerogen can effect profound, permanent changes in the antigen-specific B cell compartment independent of any influence on conventional T cell regulatory mechanisms.
D000818:Animals; D000831:Animals, Newborn; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002794:Choline / Q000031:analogs & derivatives*; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006462:Hemolytic Plaque Technique; D007108:Immune Tolerance; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010767:Phosphorylcholine / Q000276:immunology*
D007130:Immunoglobulin Idiotypes; D010767:Phosphorylcholine; D002794:Choline