Abstract
In inbred strains of mice, antiphosphorylcholine (PC) and anti-α1,3 dextran (DEX). antibodies are structurally distinct from each other and have been shown to exhibit noncrossreactive antigen binding and idiotypic specificities. However, the prototype anti-PC and anti-DEX antibodies, TEPC15 and J558, respectively, were shown to be connected via a common autoantiidiotypic monoclonal antibody isolated from newborn BALB/c mice. The capacity of various monoclonal anti-PC and anti-DEX antibodies as well as the antigens PC and DEX to modulate T15 and J558 idiotypes in BALB/c mice was tested by their administration to newborn mice. Anti-PC antibodies of the .T15 idiotype injected into 2-4-day-old mice, 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 to DEX. As a further demonstration of this connectivity, the injection of J558 into 4-day-old mice led to a down modulation of T15 idiotype, whereas both T15 and a minor idiotypeexpressing antibody M167 when injected into 8-12-day-old mice caused a reduction in expression of the J558 idiotype. As predicted from in vitro analysis, injection of anti-PC antibodies of the M167 idiotype 2 to 4 days after birth enhanced the subsequent response to PC. However, anti-PC antibodies expressing another minor M603 idiotype did not affect the PC. response. The results parallel the in vitro enhancement of M167 antibodies but not M603 on T15 binding to antiidiotype in vitro. Similarly, anti-DEX antibodies expressing the M104E idiotype had no detectable effects on the capacity to respond to PC or DEX or on the expression of T15 and J558 idiotypes as adults. Exposure of newborn mice to PC led to a dramatic reduction in the response to DEX as adults, whereas exposure to DEX at this stage of development had no effect on response to PC as adults. Collectively, these observations provide evidence for a complex functional connectivity between T15 and J558 idiotype-bearing B cells during ontogeny and extend our previous observations that development of these idiotypes is regulated by idiotype-directed interactions between B cells or their immunoglobulin products.
Highlights
In mammals, antibody responses to certain defined antigens including bacterial polysaccharides are restricted to the expansion of one or a few clones of B cells resulting in idiotypic dominance of antibodies produced by these clones in the serum (Blomberg et al, 1972; Claflin et al, 1974; Pawlak and Nisonoff, 1973; Lieberman et al, 1976;-Hansberg et ai., 1977; Mtikel/i and Karjalainen, 1977; Capra et al, 1977)
Based on the binding characteristics of these monoclonal antibodies in vitro and the demonstration that administration of these antibodies has potent longlived effects on the expression of target idiotypes in vivo (Vakil and Kearney, 1986), we proposed that B cells interact through immunoglobulin idiotypic determinants and that these interactions are involved in the establishment of the adult B-cell repertoire
We proposed that idiotypic interactions among complementary sets ot B cells during ontogeny were required for the development of T15 and J558 idiotypes
Summary
Antibody responses to certain defined antigens including bacterial polysaccharides are restricted to the expansion of one or a few clones of B cells resulting in idiotypic dominance of antibodies produced by these clones in the serum In addition to the numerous demonstrations of direct effects of polyclonal, as well as monoclonal antiidiotypic antibodies on antibody responses in vivo, evidence has accumulated for the existence of regulatory B-cell networks Based on the binding characteristics of these monoclonal antibodies in vitro and the demonstration that administration of these antibodies has potent longlived effects on the expression of target idiotypes in vivo (Vakil and Kearney, 1986), we proposed that B cells interact through immunoglobulin idiotypic determinants and that these interactions are involved in the establishment of the adult B-cell repertoire. J558-1ike B cells and a diminished capacity to respond to PC and DEX (Vakil et al, 1986) Based on these criteria, we proposed that idiotypic interactions among complementary sets ot B cells during ontogeny were required for the development of T15 and J558 idiotypes. We demonstrate that development of the dominant idiotypes T15 and J558 can be altered by neonatal exposure to the antibodies expressing either T15 or J558 idiotypes as well as antigens PC and DEXo These observations establish a functional relationship between idiotypically connected B cells and suggest that such idiotypic connections may regulate the program of repertoire development
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