A bi-directional immune network mechanism: simultaneous induction of idiotype and anti-anti-idiotype in rabbits immunized with antibody to a common idiotypic specificity of anti-VHa2-allotype antibodies.

Recently, we identified a common idiotypic specificity (IdC) present on all of the allo and auto anti-VHa2-allotype antibodies tested. In this report, we immunized allotype-matched rabbits with anti-IdC Ab. When an a1a1 homozygote was immunized with anti-IdC Ab (also from an a1a1 rabbit), two distinct Ab populations were induced which were isolated through the use of immunoadsorbent column chromatography. One of these Ab populations, adsorbed to and eluted from an insolubilized a2 IgG column, was anti-VHa2-allotype Ab (Ab 1), which reacted with a2 Ig and inhibited the reaction between the a2 allotype and anti-VHa2-allotype Ab. The other Ab population, adsorbed to and eluted from an insolubilized immunogen anti-IdC column, was anti-anti-IdC Ab (Ab 3), which was specific for the immunogen anti-IdC Ab. In another experiment, when an a1a2 heterozygous rabbit was immunized with anti-IdC Ab, only the Ab 3 was induced, which appeared to be identical to the Ab 3 induced in the a1a1 rabbit. However, when the expression of the a2 allotype in an a1a2 heterozygous rabbit was suppressed and then this rabbit was immunized with anti-IdC Ab, both Ab 1 and Ab 3 were induced. These data indicate the occurrence of a bi-directional immune response within our immune network system. According to Jerne's network theory, Ab 3 appeared to be induced through a stimulation by the idiotope of the immunogen Ab 2, whereas Ab 1 appeared to be induced through a reverse stimulation by the paratope of the immunogen Ab 2. Furthermore, the production of Ab 1 in these rabbits exhibiting the bi-directional immune response was at least 3-5 times greater than that of Ab 3 production indicating that the response through the reverse stimulation appeared to be dominant. The importance of this bi-directional immune response is discussed in this paper.