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Functional Relationship Between T15 and J558 Idiotypes in BALB/c Mice
Authors:Meenal Vakil  John F. Kearney
Affiliation:1. Division of Developmental and Clinical Immunology, Department of Microbiology, and the Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA.;2. 263 Tumor Institute, University of Alabama at Birmingham, UAB Station, Birmingham, Alabama, 35294, USA,
Abstract:In inbred strains of mice, antiphosphorylcholine (PC) and anti-α1,3 dextran (DEX). antibodiesare structurally distinct from each other and have been shown to exhibit noncrossreactiveantigen binding and idiotypic specificities. However, the prototype anti-PC andanti-DEX antibodies, TEPC15 and J558, respectively, were shown to be connected via acommon autoantiidiotypic monoclonal antibody isolated from newborn BALB/c mice. Thecapacity of various monoclonal anti-PC and anti-DEX antibodies as well as the antigens PCand DEX to modulate T15 and J558 idiotypes in BALB/c mice was tested by their administrationto newborn mice. Anti-PC antibodies of the .T15 idiotype injected into 2-4-day-oldmice, at a time when T15 anti-PC precursors develop in BALB/c mice, suppressed the anti-PC response of these mice at 6 weeks of age. Similarly, J558 antibodies injected into 8-12-day-old mice, at a time when J558 precursors normally develop, suppressed the response toDEX. As a further demonstration of this connectivity, the injection of J558 into 4-day-oldmice led to a down modulation of T15 idiotype, whereas both T15 and a minor idiotypeexpressingantibody M167 when injected into 8-12-day-old mice caused a reduction inexpression of the J558 idiotype. As predicted from in vitro analysis, injection of anti-PCantibodies of the M167 idiotype 2 to 4 days after birth enhanced the subsequent response toPC. However, anti-PC antibodies expressing another minor M603 idiotype did not affect thePC. response. The results parallel the in vitro enhancement of M167 antibodies but not M603on T15 binding to antiidiotype in vitro. Similarly, anti-DEX antibodies expressing the M104Eidiotype had no detectable effects on the capacity to respond to PC or DEX or on the expressionof T15 and J558 idiotypes as adults. Exposure of newborn mice to PC led to a dramaticreduction in the response to DEX as adults, whereas exposure to DEX at this stage ofdevelopment had no effect on response to PC as adults. Collectively, these observations provideevidence for a complex functional connectivity between T15 and J558 idiotype-bearing Bcells during ontogeny and extend our previous observations that development of these idiotypesis regulated by idiotype-directed interactions between B cells or their immunoglobulinproducts.
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