Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2
Open accessAbstract
The immunoregulatory function of the complement system has been the focus of many investigations. In particular, fragments of complement factor C3 have been shown to play a role in B-lymphocyte activation and proliferation, lymphokine production, and the generation of in vitro antibody production. Purified pneumococcal polysaccharides (PS) can induce direct activation of C3 via the alternative pathway. Using sera of C1q-deficient patients and healthy subjects, we demonstrated that C3d, a split product of C3 that is generated after degradation of iC3b, can be bound to PS antigens. The binding of C3d to PS can occur in the absence of specific antibodies. Subsequently, we showed that PS complexed with C3d can be recognized by complement receptor type 2 that is expressed on B cells. Treatment of B cells with a monoclonal antibody recognizing the C3d-binding site of complement receptor type 2 reduces the binding of PS-C3d to the cells. In addition, we showed that PS4 complexed with C3d exerted an increased immunogenicity compared with free PS4. Our results show that the complement system plays a role in the activation of PS-specific B cells, carrying membrane receptors for C3d. Consequently, the complement system plays a regulatory role in the antibody response to T-cell-independent type 2 antigens such as PS.
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- Authors
- Griffioen, A. W., Rijkers, G. T., Janssens-Korpela, P., & Zegers, B. J.
- Affiliations
- University Medical Center Utrecht (NL)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1991-05
- Volume
- 59
- Issue
- 5
- Pages
- 1839-1845
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC257924
- OpenAlex
- W2153684695
- Cited by
- 65
- References
- 39
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 1 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- pneumococcal polysaccharide, C3d, CR2, B cell activation, complement system, alternative complement pathway, immunogenicity, T-independent antigens, antibody response regulation, C1q deficiency
- MeSH terms
- Adult, Antibodies, Bacterial, Antigens, Differentiation, B-Lymphocyte, B-Lymphocytes, Complement Activation, Humans, Polysaccharides, Bacterial, Receptors, Complement, Streptococcus pneumoniae, Complement C3d, Receptors, Complement 3d
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