PMID- 7614988 OWN - NLM STAT- MEDLINE DCOM- 19950822 LR - 20061115 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 25 IP - 6 DP - 1995 Jun TI - A syngeneic idiotype is immunogenic when borne by IgM but tolerogenic when joined to IgG. PG - 1601-8 AB - Some syngeneic monoclonal antibodies (mAb) elicit immune responses like conventional T-dependent antigens. To find out whether the heavy chain class (isotype) plays a role for the immunogenicity of an idiotype (Id), we isolated rare subclones of an IgM mAb (termed Id3) in which the variable region of the heavy chain (VH) is associated with a new constant region (CH). The VH-Id3 gene is a member of the murine 36-60 family and probably has three replacement mutations. The light chain V gene is germ-line V lambda 2. IgM, IgG1, IgG2a and IgG2b variants of Id3 were purified from protein-free medium and injected without adjuvant into BALB/c mice. The parental 19S IgM mAb given subcutaneously (s.c.) elicited a vigorous humoral response against Id3; in comparison, monomeric 8S IgM was a much weaker immunogen. Unlike IgM, multiple challenges with the IgG switch variants failed to induce anti-Id3 Ab. IgG variants gained immunogenicity if they were purified from medium containing fetal calf serum, mixed with complete Freund's adjuvant or injected into mice primed with IgM-Id3. Pretreatment with 100 micrograms s.c. + 50 micrograms of the IgG2a variant extinguished the Ab response to parental IgM, but the response to adjuvant-free bovine serum albumin was intact. Therefore, the tolerance induced by the IgG2a switch variant is antigen-specific and not due to toxicity. Significant inhibition of the Ab response to parental IgM was observed after treatment with 4 micrograms of the IgG2a switch variant. Administration of the IgG1 and IgG2b switch variants also inhibited this response significantly. Thus, the outcome of an encounter with Id3 is strongly influenced by the CH isotype to which the Id is joined. This suggests novel ways to minimize unwanted Ab responses against Id of human therapeutic mAb. In the context of the theory of Id networks, we suggest that dominant B cell clones can preempt anti-Id Ab responses against themselves by early switching from IgM to IgG secretion, before immunogenic IgM Ab have had time to activate anti-Id B cells. FAU - Reitan, S K AU - Reitan SK AD - Department of Immunology, University of Tromso School of Medicine, Norway. FAU - Hannestad, K AU - Hannestad K LA - eng SI - GENBANK/X86805 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Antibodies, Anti-Idiotypic) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin M) RN - 0 (RNA, Messenger) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antibodies, Anti-Idiotypic/biosynthesis/*immunology MH - Antibody Formation/immunology MH - Base Sequence MH - Hybridomas MH - Immunization MH - Immunoglobulin G/biosynthesis/*immunology MH - Immunoglobulin M/biosynthesis/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Molecular Sequence Data MH - RNA, Messenger/analysis EDAT- 1995/06/01 00:00 MHDA- 1995/06/01 00:01 CRDT- 1995/06/01 00:00 PHST- 1995/06/01 00:00 [pubmed] PHST- 1995/06/01 00:01 [medline] PHST- 1995/06/01 00:00 [entrez] AID - 10.1002/eji.1830250620 [doi] PST - ppublish SO - Eur J Immunol. 1995 Jun;25(6):1601-8. doi: 10.1002/eji.1830250620.