Influence of a minor recurrent idiotype on the regulation of immune response: route dependence.

Sp6, a BALB/c hybridoma, produces anti-TNP IgM antibodies (AB), which carry a minor recurrent idiotype (ID). Despite the fact that only about 20% of BALB/c anti-TNP AB carry the Sp6 ID, injection of Sp6-coated spleen cells (Sp6-SC) significantly influenced the anti-TNP B cell response. Repeated intratrail (i.t.) or intravenous (i.v.) injections of Sp6-SC resulted only in a minor increase of the anti-TNP background response. When mice consecutively were challenged with TNP-horse red blood cells (HRBC), i.t. injections of Sp6-SC resulted in a 2-3-fold increase in the number of anti-TNP plaque-forming cells (PFC), while i.v. injection of Sp6-SC displayed no effect on a primary anti-TNP response. But, after i.v. as well as i.t. application of Sp6-SC, it was not possible to obtain hapten-specific suppression by i.v. injection of TNP-haptenized lymphocytes. In vitro characterization of the underlying mechanism revealed that the helper effect, which only was observed after i.t. injection, was due to a Lyt-1+ population, not adhering to Sp6-coated plates, while counterregulation of hapten-specific suppression was found in a Lyt-2+ population, adhering to Sp6-coated plates. Hence, depending on the route of priming, injection of AB with a recurrent ID can augment the response towards the nominal antigen either directly via activation of helper cells or indirectly via activation of counterregulatory cells.