CELLULAR IMMUNOLOGY 67, 334-345 (1982) Lack of Involvement of Auto-anti-idiotypic Antibody in the Regulation of Oscillations and Tolerance in the Antibody Response to Levan’ JACQUES R. HIERNAUX,* JUDY CHIANG,* PHILLIP J. BAKER,**~ CHARLES DELISI,~ AND BENJAMIN PRESCOTT$ *Laboratory of Microbial Immunity, National Institute of Allergy and Infectious Diseases, and the tLaboratory of Theoretical Biology, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20205, and the SBiomedical Research Institute. Rockville, Maryland 20850 Received December 2. 1981; accepted January 3, 1982 Bacterial levan (BL) induces a cyclic (oscillatory) antibody response in both euthymic and athymic BALB/c mice. Significant numbers of plaque-forming cells (PFC) making auto-anti- idiotypic antibody directed against a major cross-reactive idiotype expressed on antibodies specific for BL were detected in euthymic-but not athymic-mice. This suggests that auto- anti-idiotypic antibody, the formation of which requires the participation of mature T cells, does not play a decisive role in generating the cyclic patterns observed. However, such antibody might still influence the proportion of PFC making antibody of complementary idiotype. No relationship between the suppressive property of auto-anti-idiotypic antibody and either the induction or maintenance of immunological tolerance to BL was evident. INTRODUCTION Since Jerne developed the concept of immune networks (l), the role of idiotypic interactions in regulating the immune response has been studied extensively for a variety of antigenic systems (for a review, see Ref. (2)). Deliberate perturbations of the idiotypic equilibrium, by means of the inoculation of a given idiotype or the injection of specific anti-idiotypic antibody, can lead to the suppression (3-5) or expansion (6-9) of clones expressing a complementary idiotype. Since the idiotypic network is assumed to be functional (l), regulatory auto-anti-idiotypic antibody or cells should be detected during the course of an immune response and their occurrence should be related to the generation of tolerance (10) or immune mem- ory (11). The detection of auto-anti-idiotypic antibodies has been reported in various ex- perimental systems (12-18). Their occurrence usually coincides with a decrease in the expression of a complementary idiotype, which seems to indicate that auto- anti-idiotypic antibodies tend to suppress immune responses.This suggests one of several mechanisms for the induction and/or the maintenance of tolerance (19), I This work was supported in part through funds available from the National Institute of Allergy and Infectious Diseases (National Institutes of Health) Contract 263-80-D-0394. 2 Send proofs and correspondence to Dr. P. J. Baker, LMI, NIAID, National Institutes of Health, Building 5, Room 235, Bethesda, Maryland 20205. 334 OOOS-8749/82/040334-12.$02.00/0 Copyright Q 1982 by Academic Prrcs, Inc. AU rights of reproduction in any form reserved.