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

Abstract

Sp6, a BALB/c hybridoma, produces anti-TNP IgM antibodies (AB), which carry a minor recurrent idiotype (ID) (1). 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), Lt. 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 TNPhaptenized lymphocytes (2). 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.