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Role of repetitive antigen patterns for induction of antibodies against antibodies.

Fehr T, Bachmann MF, Bucher E, Kalinke U, Di Padova FE, Lang AB, Hengartner H, Zinkernagel RM - J. Exp. Med. (1997)

Bottom Line: Why and how such anti-antibodies are induced during autoimmune diseases, has remained largely unclear.We present evidence that antibodies bound to strictly ordered, but not to irregularly arranged, antigens dramatically enhance induction of anti-antibodies, already after a single immunization and without using adjuvants.The results indicate a novel link between anti-antibody responses and infectious agents, and suggest a similar role for repetitive self-antigens such as DNA or collagen involved in chronic immunopathological diseases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental Immunology, University of Zürich, CH-8091 Zürich, Switzerland.

ABSTRACT
Antibody responses against antibodies, such as rheumatoid factors, are found in several immunopathological diseases and may play a role in disease pathogenesis. Experience shows that they are usually difficult to induce experimentally. Antibodies specific for immunoglobulin constant regions (anti-allotypic) or for variable regions (anti-idiotypic) have been investigated in animal models; the latter have even been postulated to regulate antibody and T cell responses via network-like interactions. Why and how such anti-antibodies are induced during autoimmune diseases, has remained largely unclear. Because repetitively arranged epitopes in a paracrystalline structure of a viral envelope cross-link B cell receptors efficiently to induce a prompt T-independent IgM response, this study used immune complexes containing viruses or bacteria to evaluate the role of antigen pattern for induction of anti-antibody responses. We present evidence that antibodies bound to strictly ordered, but not to irregularly arranged, antigens dramatically enhance induction of anti-antibodies, already after a single immunization and without using adjuvants. The results indicate a novel link between anti-antibody responses and infectious agents, and suggest a similar role for repetitive self-antigens such as DNA or collagen involved in chronic immunopathological diseases.

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In vivo half-life of  an IgM antibody (M5) in mice  with or without anti-antibody titers. A/J (closed symbols) or  BALB/c mice (open symbols)  were twice (interval, 14 d) injected with VSV-NJ/M3 IC to  induce anti-antibodies. 10 d after  the second injection these mice  (squares) and not immunized  controls (diamonds) were injected with 5 μg of anti-VSVIND IgM (M5), and VSV-IND  neutralizing titers were measured  at the indicated timepoints. In  vivo half-life of M5 was determined by regression analysis.
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Figure 2: In vivo half-life of an IgM antibody (M5) in mice with or without anti-antibody titers. A/J (closed symbols) or BALB/c mice (open symbols) were twice (interval, 14 d) injected with VSV-NJ/M3 IC to induce anti-antibodies. 10 d after the second injection these mice (squares) and not immunized controls (diamonds) were injected with 5 μg of anti-VSVIND IgM (M5), and VSV-IND neutralizing titers were measured at the indicated timepoints. In vivo half-life of M5 was determined by regression analysis.

Mentions: VSV-IND neutralizing antibodies (Fig. 2) were determined on the indicated timepoints by a plaque reduction assay on Vero cells as described before (26). Titers are indicated as -log2 of 40-fold prediluted sera.


Role of repetitive antigen patterns for induction of antibodies against antibodies.

Fehr T, Bachmann MF, Bucher E, Kalinke U, Di Padova FE, Lang AB, Hengartner H, Zinkernagel RM - J. Exp. Med. (1997)

In vivo half-life of  an IgM antibody (M5) in mice  with or without anti-antibody titers. A/J (closed symbols) or  BALB/c mice (open symbols)  were twice (interval, 14 d) injected with VSV-NJ/M3 IC to  induce anti-antibodies. 10 d after  the second injection these mice  (squares) and not immunized  controls (diamonds) were injected with 5 μg of anti-VSVIND IgM (M5), and VSV-IND  neutralizing titers were measured  at the indicated timepoints. In  vivo half-life of M5 was determined by regression analysis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196322&req=5

Figure 2: In vivo half-life of an IgM antibody (M5) in mice with or without anti-antibody titers. A/J (closed symbols) or BALB/c mice (open symbols) were twice (interval, 14 d) injected with VSV-NJ/M3 IC to induce anti-antibodies. 10 d after the second injection these mice (squares) and not immunized controls (diamonds) were injected with 5 μg of anti-VSVIND IgM (M5), and VSV-IND neutralizing titers were measured at the indicated timepoints. In vivo half-life of M5 was determined by regression analysis.
Mentions: VSV-IND neutralizing antibodies (Fig. 2) were determined on the indicated timepoints by a plaque reduction assay on Vero cells as described before (26). Titers are indicated as -log2 of 40-fold prediluted sera.

Bottom Line: Why and how such anti-antibodies are induced during autoimmune diseases, has remained largely unclear.We present evidence that antibodies bound to strictly ordered, but not to irregularly arranged, antigens dramatically enhance induction of anti-antibodies, already after a single immunization and without using adjuvants.The results indicate a novel link between anti-antibody responses and infectious agents, and suggest a similar role for repetitive self-antigens such as DNA or collagen involved in chronic immunopathological diseases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Experimental Immunology, University of Zürich, CH-8091 Zürich, Switzerland.

ABSTRACT
Antibody responses against antibodies, such as rheumatoid factors, are found in several immunopathological diseases and may play a role in disease pathogenesis. Experience shows that they are usually difficult to induce experimentally. Antibodies specific for immunoglobulin constant regions (anti-allotypic) or for variable regions (anti-idiotypic) have been investigated in animal models; the latter have even been postulated to regulate antibody and T cell responses via network-like interactions. Why and how such anti-antibodies are induced during autoimmune diseases, has remained largely unclear. Because repetitively arranged epitopes in a paracrystalline structure of a viral envelope cross-link B cell receptors efficiently to induce a prompt T-independent IgM response, this study used immune complexes containing viruses or bacteria to evaluate the role of antigen pattern for induction of anti-antibody responses. We present evidence that antibodies bound to strictly ordered, but not to irregularly arranged, antigens dramatically enhance induction of anti-antibodies, already after a single immunization and without using adjuvants. The results indicate a novel link between anti-antibody responses and infectious agents, and suggest a similar role for repetitive self-antigens such as DNA or collagen involved in chronic immunopathological diseases.

Show MeSH
Related in: MedlinePlus