Limits...
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.

Show MeSH

Related in: MedlinePlus

IgG-mediated suppression of primary IgM-responses in Cr2 KO mice.Cr2 KO and BALB/c mice were immunized with 50 μg IgGb anti-SRBC and 5x107 SRBC, SRBC alone, or IgG alone. 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 together with SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were: BALB/c, 76,208; Cr2 KO, 11,015. Data are pooled from three experiments; (n = 4/group in each experiment). p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. ***, p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664261&req=5

pone.0143841.g002: IgG-mediated suppression of primary IgM-responses in Cr2 KO mice.Cr2 KO and BALB/c mice were immunized with 50 μg IgGb anti-SRBC and 5x107 SRBC, SRBC alone, or IgG alone. 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 together with SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were: BALB/c, 76,208; Cr2 KO, 11,015. Data are pooled from three experiments; (n = 4/group in each experiment). p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. ***, p < 0.001.

Mentions: To address whether CR1/2 are required for the suppressive function of passively administered IgG, BALB/c and Cr2 KO mice were immunized with IgGb anti-SRBC and SRBC, SRBC alone, or IgG alone. IgG suppressed 98% or more of IgM-responses both in BALB/c wildtype controls and Cr2 KO mice (Fig 2) and IgG also efficiently suppressed the IgG anti-SRBC response in BALB/c controls (Figure G in S1 Fig). Cr2 KO mice have impaired antibody responses to antigens administered alone [17, 23, 25]. Therefore, as expected, Cr2 KO mice given SRBC alone produced very low levels of IgG anti-SRBC, both when assayed at a serum dilution of 1:625 with a substrate incubation during 30 min (Figure H in S1 Fig) and at a serum dilution of 1:25 with a substrate incubation during 3 h (Figure I in S1 Fig). Therefore, no conclusions regarding the ability of IgG to suppress the IgG-response in Cr2 KO mice could be drawn.


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-responses in Cr2 KO mice.Cr2 KO and BALB/c mice were immunized with 50 μg IgGb anti-SRBC and 5x107 SRBC, SRBC alone, or IgG alone. 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 together with SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were: BALB/c, 76,208; Cr2 KO, 11,015. Data are pooled from three experiments; (n = 4/group in each experiment). p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. ***, p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664261&req=5

pone.0143841.g002: IgG-mediated suppression of primary IgM-responses in Cr2 KO mice.Cr2 KO and BALB/c mice were immunized with 50 μg IgGb anti-SRBC and 5x107 SRBC, SRBC alone, or IgG alone. 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 together with SRBC. Direct PFC/spleen in the respective control groups (receiving antigen alone) were: BALB/c, 76,208; Cr2 KO, 11,015. Data are pooled from three experiments; (n = 4/group in each experiment). p-values denote comparisons between mice immunized with IgG anti-SRBC together with SRBC and mice immunized with SRBC alone. ***, p < 0.001.
Mentions: To address whether CR1/2 are required for the suppressive function of passively administered IgG, BALB/c and Cr2 KO mice were immunized with IgGb anti-SRBC and SRBC, SRBC alone, or IgG alone. IgG suppressed 98% or more of IgM-responses both in BALB/c wildtype controls and Cr2 KO mice (Fig 2) and IgG also efficiently suppressed the IgG anti-SRBC response in BALB/c controls (Figure G in S1 Fig). Cr2 KO mice have impaired antibody responses to antigens administered alone [17, 23, 25]. Therefore, as expected, Cr2 KO mice given SRBC alone produced very low levels of IgG anti-SRBC, both when assayed at a serum dilution of 1:625 with a substrate incubation during 30 min (Figure H in S1 Fig) and at a serum dilution of 1:25 with a substrate incubation during 3 h (Figure I in S1 Fig). Therefore, no conclusions regarding the ability of IgG to suppress the IgG-response in Cr2 KO mice could be drawn.

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