INDUCTION OF A NONOSCILLATING, LONG-LASTING HUMORAL IMMUNE-RESPONSE TO AN INTERNAL NETWORK ANTIGEN

B lymphocyte antigen receptors form an internal idiotypic network whic h is also connected by idiotypic interactions with the T lymphocyte co mpartment. Idiotypic-anti-idiotypic activation of lymphocytes has main ly been measured at the cellular level while the kinetics of primary a nti-idiotypic humoral responses has so far not been determined, Here, we describe the induction of an anti-idiotypic immune response to the major idiotype (Id(Ox1)) of the primary immune response in BALB/c mice to the hapten 2-phenyl-5-oxazolone coupled to chicken serum albumin, A primary anti-idiotypic humoral response could be induced with the ph Ox-binding and Id(Ox1)-expressing, germline-encoded antibody H11.5 (mu , kappa) coupled to keyhole limpet hemocyanin. Compared to that of con ventional antigens, the anti-idiotypic response showed a lag phase of 3 weeks, When the anti-Id(Ox1) serum titers had declined to background levels, a secondary anti-Id(Ox1) response could be induced even with soluble H11.5, This response showed as fast an increase as conventiona l antigens, but the antibody plateau did not exceed that of the primar y response, During this secondary anti-Id(Ox1) response and probably t o a small extent also during the primary response, the mice developed an idiotypically non-related IgM-anti-phOx response. In contrast, solu ble H11.5-either passively injected or transiently expressed during th e early primary anti-hapten response-suppressed the anti-idiotypic res ponse to H11.5 for up to 7 months in the majority of mice, while indiv idual 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 idio typic network regulation are discussed.