Second symmetry in the BALB/c‐C57BL/6 (B6) system, and anti‐antiself antibodies in ageing B6 mice

Al-Fahim, Abdulaziz; Hoffmann, Geoffrey W.

doi:10.1046/j.1440-1711.1998.00711.x

Cited by 2 publications

(1 citation statement)

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“…Similarly, the antigen-specific antibodies in a B anti-A serum are specific for the anti-idiotypic antibodies (A anti-anti-A) in an A anti-B serum. This set of relationships is known as “second symmetry” [6,24]. (“First symmetry” in the symmetrical immune network theory is the concept that if an idiotype A is anti-idiotypic to an idiotype B, the idiotype B is anti-idiotypic to the idiotype A; reviewed in [6]).…”

Section: Resultsmentioning

confidence: 99%

Toward a New Kind of Vaccine: A Logical Extension of the Symmetrical Immune Network Theory

Gorczynski¹,

Hoffmann²

2017

Interact J Med Res

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BackgroundThe symmetrical immune network theory, developed in 1975, is based on the existence of specific T cell factors and hypothesizes that normal IgG immune responses comprise the production of 2 kinds of antibodies, namely antigen-specific antibodies and anti-idiotypic antibodies.ObjectiveThe aim of this study was to confirm the existence of specific T cells factors and to show that immunization of C3H mice with BL/6 skin or using nominal antigen for immunization (Tetanus Toxoid) induced production of antigen-specific (anti-BL/6 or antitetanus) antibodies plus anti-idiotypic antibodies (C3H anti-anti-C3H). Subsequently, we investigated the role of combinations of antigen-specific and anti-idiotype antibodies in a variety of animal models of clinical diseases.MethodsAntigen-specific antibodies were produced by conventional immunization of mice (eg, with tetanus toxoid or by skin allografting). Subsequent anti-idiotypic antibodies were derived by exhaustive absorption of antigen-specific antibody, with confirmation of anti-idiotypic specificity by binding to relevant target antigen-specific antibodies in an enzyme-linked immunosorbent assay (ELISA). Antigen-specific plus anti-idiotypic antibodies were then used to modulate skin allograft survival, dextran sulfate sodium (DSS)-induced colitis, ovalbumin (OVA)-induced IgE production, and breast cancer growth in mice.ResultsInfusions of anti-BL/6 antibodies together with BL/6 anti-anti-BL/6 antibodies specifically suppressed (>85%) an immune response to BL/6 lymphocytes in C3H mice. The two kinds of antibodies with complementary specificity are hypothesized to stimulate 2 populations of T lymphocytes. Coselection of these 2 populations leads to a new stable steady state of the system with diminished reactivity to BL/6 tissue. A combination of anti-C3H and C3H anti‑anti-C3H IgG antibodies down-regulated inflammation in a mouse model of inflammatory bowel disease (>75%) and attenuated anti-IgE production and sensitization to produce IL4 cytokines (>70%) in an OVA-allergy model. Combination of C3H anti‑BL/6 and BL/6 anti-anti-BL/6 antibodies decreased tumor growth and metastases (>705) in an EMT6 transplantable breast cancer model.ConclusionsUse of a combination of antigen-specific and anti-idiotypic antibodies has potential as a new class of vaccines.

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Section: Resultsmentioning

confidence: 99%

Toward a New Kind of Vaccine: A Logical Extension of the Symmetrical Immune Network Theory

Gorczynski¹,

Hoffmann²

2017

Interact J Med Res

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Towards a new kind of vaccine

Hoffmann¹,

Gorczynski

2017

Preprint

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We present new data showing that normal IgG immune responses comprise the production of two kinds of antibodies, namely anti-foreign and anti-anti-self antibodies. For example, immunization of C3H mice by two rounds of BL/6 skin grafting results in the production of anti-BL/6 antibodies plus antiidiotypic antibodies (C3H anti-anti-C3H) with the latter being detected using antibodies produced in a BL/6 anti-C3H immune response. Similarly, the IgG immune response of C3H mice to tetanus toxoid includes the production of C3H anti-anti-C3Hantibodies. Antigen-specific antibodies produced in one alloimmunization plus antiidiotypic antibodies produced in the converse immunization can be used to synergistically induce specific tolerance. We show that infusions of anti-BL/6 antibodies together with BL/6 anti-anti-BL/6 antibodies specifically suppress an immune response to BL/6 lymphocytes in C3H mice. Specific tolerance was measured as suppression of the induction of BL/6-specific cytotoxic T cells. The two kinds of antibodies with complementary specificity are believed to stimulate two populations of T lymphocytes, and co-selection (mutual selection) of these two populations leads to a new stable steady state of the system that has specifically diminished reactivity to BL/6 tissue. Stimulation with a combination of anti-C3H and C3H anti-anti-C3H IgG antibodies furthermore down-regulates inflammation in a mouse model of inflammatory bowel disease.An analogous combination of C3H anti-BL/6 and BL/6 anti-anti-BL/6 antibodies significantly down-regulates tumour growth and metastases in BALB/c mice in the EMT6 transplantable . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/101345 doi: bioRxiv preprint first posted online Jan. 18, 2017; breast cancer model. We conclude that a combination of certain antigen-specific and antiidiotypic antibodies has potential as a new class of vaccines based on the symmetrical immune network theory. This new kind of vaccine does not involve the production of antibodies. The prevention of two important degenerative diseases makes this a potential antiaging technology.

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Second symmetry in the BALB/c‐C57BL/6 (B6) system, and anti‐antiself antibodies in ageing B6 mice

Cited by 2 publications

References 20 publications

Toward a New Kind of Vaccine: A Logical Extension of the Symmetrical Immune Network Theory

Toward a New Kind of Vaccine: A Logical Extension of the Symmetrical Immune Network Theory

Towards a new kind of vaccine

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