Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope
Surface antibody maturation - Affinity maturation in B cells generates antibodies with increasingly enhanced antigen-binding properties. Imkeller et al. investigated the maturation of human B cells that express protective antibodies against the circumsporozoite protein of the malaria-causing parasit...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
22 Jun 2018
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| In: |
Science
Year: 2018, Volume: 360, Issue: 6395, Pages: 1358-1362 |
| ISSN: | 1095-9203 |
| DOI: | 10.1126/science.aar5304 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1126/science.aar5304 Verlag: https://science.sciencemag.org/content/360/6395/1358 
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| Author Notes: | Katharina Imkeller, Stephen W. Scally, Alexandre Bosch, Gemma Pidelaserra Martí, Giulia Costa, Gianna Triller, Rajagopal Murugan, Valerio Renna, Hassan Jumaa, Peter G. Kremsner, B. Kim Lee Sim, Stephen L. Hoffman, Benjamin Mordmüller, Elena A. Levashina, Jean-Philippe Julien, Hedda Wardemann |
| Summary: | Surface antibody maturation - Affinity maturation in B cells generates antibodies with increasingly enhanced antigen-binding properties. Imkeller et al. investigated the maturation of human B cells that express protective antibodies against the circumsporozoite protein of the malaria-causing parasite Plasmodium falciparum (PfCSP). The repetitive structure of PfCSP induces mutations in B cells, facilitating direct interactions between two repeat-bound antibodies against PfCSP, which enhance antigen affinity and B cell activation. Such interactions may optimize binding and promote clustering of surface antibodies in general. - Science, this issue p. 1358 - Affinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens. - A repetitive malaria antigen induces clonal selection and affinity maturation of human B cells expressing protective antibodies. - A repetitive malaria antigen induces clonal selection and affinity maturation of human B cells expressing protective antibodies. |
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| Item Description: | Gesehen am 23.01.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1095-9203 |
| DOI: | 10.1126/science.aar5304 |