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IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors.

Bergström JJ, Heyman B - PLoS ONE (2015)

Bottom Line: This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally.The mechanisms by which IgG suppresses antibody responses are poorly understood.In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.

ABSTRACT
Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs) are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC), was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice) or FcγRI, III, and IV (FcRγ knockout mice). Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice), C3 (C3 knockout mice), or complement receptors 1 and 2 (Cr2 knockout mice) as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes.

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IgG-mediated suppression of primary IgM- and IgG-responses in FcγRIIB KO and FcRγ KO mice.FcγRIIB KO, FcRγ KO, and BALB/c mice were immunized with 10 μg IgGb anti-SRBC and 5x106 SRBC, SRBC alone, or IgG alone. (A,C) Five days after immunization, the number of spleen cells producing IgM anti-SRBC was assayed. Responses are shown as percentage of the direct PFC response/spleen in mice given SRBC alone (100%, open bars); black bars show responses in mice given IgG and SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were in A: BALB/c, 12,218; FcγRIIB KO, 36,391 (p<0.05) and in C: BALB/c, 57,279; FcRγ KO 40,831. (B,D) Seven to 49 days later, serum levels of IgG anti-SRBC were assayed in ELISA on sera diluted 1:625. Data are representative of one (A, C) or pooled from three (B, D) experiments with each KO strain. p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. **, p < 0.01; ***, p < 0.001.
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pone.0143841.g003: IgG-mediated suppression of primary IgM- and IgG-responses in FcγRIIB KO and FcRγ KO mice.FcγRIIB KO, FcRγ KO, and BALB/c mice were immunized with 10 μg IgGb anti-SRBC and 5x106 SRBC, SRBC alone, or IgG alone. (A,C) Five days after immunization, the number of spleen cells producing IgM anti-SRBC was assayed. Responses are shown as percentage of the direct PFC response/spleen in mice given SRBC alone (100%, open bars); black bars show responses in mice given IgG and SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were in A: BALB/c, 12,218; FcγRIIB KO, 36,391 (p<0.05) and in C: BALB/c, 57,279; FcRγ KO 40,831. (B,D) Seven to 49 days later, serum levels of IgG anti-SRBC were assayed in ELISA on sera diluted 1:625. Data are representative of one (A, C) or pooled from three (B, D) experiments with each KO strain. p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. **, p < 0.01; ***, p < 0.001.

Mentions: FcγRIIB KO and BALB/c mice were immunized with IgGb anti-SRBC and SRBC, SRBC alone, or IgGb alone. IgG efficiently suppressed the IgM response in both strains (Fig 3A). Using the allotype ELISA system described above, it was shown that IgG suppressed also longterm IgG-responses in FcγRIIB KO as well as in BALB/c wildtype controls (Fig 3B). Noteworthy is that FcγRIIB KO mice, immunized with SRBC alone, generated higher IgM anti-SRBC responses than BALB/c wildtype mice (Fig 3A legend). This finding confirms the negatively regulating effect of FcγRIIB on antibody responses previously reported [26]. In summary, efficient suppression of IgM and IgG responses by specific IgG takes place in the absence of FcγRIIB.


IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors.

Bergström JJ, Heyman B - PLoS ONE (2015)

IgG-mediated suppression of primary IgM- and IgG-responses in FcγRIIB KO and FcRγ KO mice.FcγRIIB KO, FcRγ KO, and BALB/c mice were immunized with 10 μg IgGb anti-SRBC and 5x106 SRBC, SRBC alone, or IgG alone. (A,C) Five days after immunization, the number of spleen cells producing IgM anti-SRBC was assayed. Responses are shown as percentage of the direct PFC response/spleen in mice given SRBC alone (100%, open bars); black bars show responses in mice given IgG and SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were in A: BALB/c, 12,218; FcγRIIB KO, 36,391 (p<0.05) and in C: BALB/c, 57,279; FcRγ KO 40,831. (B,D) Seven to 49 days later, serum levels of IgG anti-SRBC were assayed in ELISA on sera diluted 1:625. Data are representative of one (A, C) or pooled from three (B, D) experiments with each KO strain. p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. **, p < 0.01; ***, p < 0.001.
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Related In: Results  -  Collection

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pone.0143841.g003: IgG-mediated suppression of primary IgM- and IgG-responses in FcγRIIB KO and FcRγ KO mice.FcγRIIB KO, FcRγ KO, and BALB/c mice were immunized with 10 μg IgGb anti-SRBC and 5x106 SRBC, SRBC alone, or IgG alone. (A,C) Five days after immunization, the number of spleen cells producing IgM anti-SRBC was assayed. Responses are shown as percentage of the direct PFC response/spleen in mice given SRBC alone (100%, open bars); black bars show responses in mice given IgG and SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were in A: BALB/c, 12,218; FcγRIIB KO, 36,391 (p<0.05) and in C: BALB/c, 57,279; FcRγ KO 40,831. (B,D) Seven to 49 days later, serum levels of IgG anti-SRBC were assayed in ELISA on sera diluted 1:625. Data are representative of one (A, C) or pooled from three (B, D) experiments with each KO strain. p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. **, p < 0.01; ***, p < 0.001.
Mentions: FcγRIIB KO and BALB/c mice were immunized with IgGb anti-SRBC and SRBC, SRBC alone, or IgGb alone. IgG efficiently suppressed the IgM response in both strains (Fig 3A). Using the allotype ELISA system described above, it was shown that IgG suppressed also longterm IgG-responses in FcγRIIB KO as well as in BALB/c wildtype controls (Fig 3B). Noteworthy is that FcγRIIB KO mice, immunized with SRBC alone, generated higher IgM anti-SRBC responses than BALB/c wildtype mice (Fig 3A legend). This finding confirms the negatively regulating effect of FcγRIIB on antibody responses previously reported [26]. In summary, efficient suppression of IgM and IgG responses by specific IgG takes place in the absence of FcγRIIB.

Bottom Line: This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally.The mechanisms by which IgG suppresses antibody responses are poorly understood.In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.

ABSTRACT
Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs) are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC), was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice) or FcγRI, III, and IV (FcRγ knockout mice). Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice), C3 (C3 knockout mice), or complement receptors 1 and 2 (Cr2 knockout mice) as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes.

Show MeSH
Related in: MedlinePlus