In vivo inhibition of the antibody response by a complement receptor-specific monoclonal antibody.

Heyman, Birgitta; Wiersma, Erik J.; Kinoshita, Taroh

doi:10.1084/jem.172.2.665

Cited by 191 publications

(117 citation statements)

References 14 publications

(11 reference statements)

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“…Subsequent studies showed that Ab responses were also severely impaired in C4-deficient humans (5), guinea pigs (6,7), and mice (8); C2-deficient guinea pigs (7); and C3-deficient dogs (9) and mice (8). Generally, the Ab response to lower antigen (Ag) doses is more dependent on C than responses to higher doses (9,10). Lack of C5 was compatible with normal Ab responses (11), excluding involvement of the later C factors as well as the lytic pathway.…”

Section: Igm Mutation | Natural Igmmentioning

confidence: 90%

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

Rutemark

Alicot

Bergman

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Animals lacking complement factors C1q, C2, C3, or C4 have severely impaired Ab responses, suggesting a major role for the classic pathway. The classic pathway is primarily initiated by antigen–Ab complexes. Therefore, its role for primary Ab responses seems paradoxical because only low amounts of specific Abs are present in naive animals. A possible explanation could be that the classic pathway is initiated by IgM from naive mice, binding with sufficient avidity to the antigen. To test this hypothesis, a knock-in mouse strain, Cμ13, with a point mutation in the gene encoding the third constant domain of the μ-heavy chain was constructed. These mice produce IgM in which proline in position 436 is substituted with serine, a mutation previously shown to abrogate the ability of mouse IgM to activate complement. Unexpectedly, the Ab response to sheep erythrocytes and keyhole limpet hemocyanin in Cμ13 mice was similar to that in WT mice. Thus, although secreted IgM and the classic pathway activation are both required for the normal primary Ab response, this does not require that IgM activate C. This led us to test Ab responses in animals lacking one of three other endogenous activators of the classic pathway: specific intracellular adhesion molecule-grabbing nonintegrin R1, serum amyloid P component, and C-reactive protein. Ab responses were also normal in these animals.

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Section: Igm Mutation | Natural Igmmentioning

confidence: 90%

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

Rutemark

Alicot

Bergman

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Biotinylated proteins were detected using streptavidin-HRP (Pierce Chemicals). 35 S-Labeled molecules were quantified with a PhosphorImager (Amersham Biosciences).…”

Section: Immunoprecipitationsmentioning

confidence: 99%

B Cell Receptors and Complement Receptors Target the Antigen to Distinct Intracellular Compartments

Perrin-Cocon

Villiers

Salamero

et al. 2004

The Journal of Immunology

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The processing of exogenous Ags is an essential step for the generation of immunogenic peptides that will be presented to T cells. This processing relies on the efficient intracellular targeting of Ags, because it depends on the content of the compartments in which Ags are delivered in APCs. Opsonization of Ags by the complement component C3 strongly enhances their presentation by B cells and increases their immunogenicity in vivo. To investigate the role of C3 in the targeting of Ags, we compared the intracellular traffic of proteins internalized by complement receptor (CR) and B cell receptor (BCR) in B lymphocytes. Whereas both receptors are able to induce efficient Ag presentation, their intracellular pathways are different. CR ligand is delivered to compartments containing MHC class II molecules (MHC-II) but devoid of transferrin receptor and Lamp-2, whereas BCR rapidly targets its ligand toward Lamp-2-positive, late endosomal MHC-II-enriched compartments through intracellular vesicles containing transferrin receptor. CR and BCR are delivered to distinct endocytic pathways, and the kinetic evolution of the protein content of these pathways is very different. Both types of compartments contain MHC-II, but CR-targeted compartments receive less neosynthesized MHC-II than do BCR-targeted compartments. The targeting induced by CR toward compartments that are distinct from BCR-targeted compartments probably participates in C3 modulation of Ag presentation.

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“…Several lines of evidence prove the role of the activation fragments of the third component (C3) and their receptors, namely complement receptor type 1 (CR1) 3 and type 2 (CR2), in directing and regulating adaptive immune responses. In mice, C3 has been shown indispensable to the development of an effective Ab response (5) and CR1/2-specific Abs were demonstrated to inhibit Ab production by B cells (6). In the germinal centers, follicular dendritic cells expressing CR1/2 can localize complementcoated Ags on their surface, thus, providing a positive signal for B cell survival and generation of memory B cells (7)(8)(9).…”

mentioning

confidence: 99%

Complement Receptor Type 1 (CD35) Mediates Inhibitory Signals in Human B Lymphocytes

Józsi¹,

Prechl

Bajtay

et al. 2002

The Journal of Immunology

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The complement system—particularly component C3—has been demonstrated to be a key link between innate and adaptive immunity. The trimolecular complex of complement receptor type 2 (CR2), CD19, and CD81 is known to promote B cell activation when coligated with the B cell Ag receptor. In the present study, we aimed to elucidate the role of human complement receptor type 1 (CR1), the other C3-receptor on B cells. As ligand, aggregated C3 and aggregated C3(H2O), i.e., multimeric “C3b-like C3”, are used, which bind to CR1, but not to CR2. In experiments studying the functional consequences of CR1-clustering, the multimeric ligand is shown to inhibit the proliferation of tonsil B cells activated with a suboptimal dose of anti-IgM F(ab′)2. Importantly, this inhibitory activity also occurs in the presence of the costimulatory cytokines IL-2 and IL-15. The anti-IgM-induced transient increase in the concentration of intracellular free Ca2+ and phosphorylation of several cytoplasmic proteins are strongly reduced in the presence of the CR1 ligand. Data presented indicate that CR1 has a negative regulatory role in the B cell Ag receptor mediated activation of human B lymphocytes.

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In vivo inhibition of the antibody response by a complement receptor-specific monoclonal antibody.

Cited by 191 publications

References 14 publications

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

B Cell Receptors and Complement Receptors Target the Antigen to Distinct Intracellular Compartments

Complement Receptor Type 1 (CD35) Mediates Inhibitory Signals in Human B Lymphocytes

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