Anti-idiotypic immune responses against adjuvant-free isologous IgM monoclonal antibodies and their augmentation by complex formation between IgM and albumin in bovine serum.
In previous studies we demonstrated that the hypermutated isologous myeloma protein MOPC 315 (isotype IgA; lambda 2) is recognized by T helper cells like an ordinary foreign protein antigen. To what extent can an immune system recognize and respond to V domains from the primary (pre-immune) repertoire? To study this question we made 21 BALB/c hybridoma anti-2,4,6 trinitrophenyl monoclonal antibodies (mAb) of IgM; lambda isotype. All mAb purified from supernatants containing fetal bovine serum had formed spontaneous complexes with bovine serum albumin possibly by way of disulfide interchange. Twenty of twenty-one mAb from this source elicited IgG1 anti-idiotypic (Id) Ab when given as a single adjuvant-free dose of 200 micrograms. For 12 of them even 10 micrograms was sufficient. This indicated that BSA augmented the anti-Id responses by a carrier effect. Three of the mAb were therefore purified from ascites fluid and from serum-free medium. Only one of them then induced humoral anti-Id responses in BALB/c mice when given as a single adjuvant-free dose of 100 micrograms. The other two became immunogenic when emulsified in Freund's complete adjuvant. The results indicate that some IgM mAb exist whose Id determinants alone can elicit substantial anti-Id responses because they are recognized like ordinary foreign protein antigens. Since albumin in fetal bovine serum forms complexes with IgM and greatly augments its immunogenicity, serum-free medium should be used for production of human or humanized therapeutic IgM mAb. A possible role for Id for IgM Ab as cardinal autoantigens is discussed.
Hannestad
K
K
Department of Immunology, University of Tromsø, School of Medicine, Norway.
Andreassen
K
K
Kristoffersen
G
G
D000276:Adjuvants, Immunologic; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology*; D007328:Insulin / Q000276:immunology; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D012710:Serum Albumin, Bovine / Q000276:immunology; D013997:Time Factors; D014301:Trinitrobenzenes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D007328:Insulin; D046911:Macromolecular Substances; D014301:Trinitrobenzenes; D012710:Serum Albumin, Bovine