Induction of a non-oscillating, long-lasting humoral immune response to an internal network antigen

B lymphocyte antigen receptors form an internal idiotypic network which is also connected by idiotypic interactions with the T lymphocyte compartment. Idiotypic-anti-idiotypic activation of lymphocytes has mainly been measured at the cellular level while the kinetics of primary anti-idiotypic humoral responses has so far not been determined. Here, we describe the induction of an anti-idiotypic immune response to the major idiotype (IdOx1) of the primary immune response in BALB/c mice to the hapten 2-phenyl-t-oxazolone coupled to chicken serum albumin. A primary anti-idiotypic humoral response could be induced with the phOx-binding and IdOx1-expressing, germline-encoded antibody H11.5 (mu, kappa) coupled to keyhole limpet hemocyanin. Compared to that of conventional antigens, the anti-idiotypic response showed a lag phase of 3 weeks. When the anti-IdOx1 serum titers had declined to background levels, a secondary anti-IdOx1 response could be induced even with soluble H11.5. This response showed as fast an increase as conventional antigens, but the antibody plateau did not exceed that of the primary response. During this secondary anti-IdOx1 response and probably to a small extent also during the primary response, the mice developed an idiotypically non-related IgM-anti-phOx response. In contrast, soluble H11.5 - either passively injected or transiently expressed during the early primary anti-hapten response - suppressed the anti-idiotypic response to H11.5 for up to 7 months in the majority of mice, while individual mice exhibited an early release from this suppression at various times. The differences and similarities between external and internal antigen-induced immune responses as well as the implications for idiotypic network regulation are discussed.