About: Public antibodies to malaria antigens generated by two LAIR1 insertion modalities

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About: Public antibodies to malaria antigens generated by two LAIR1 insertion modalities Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Public antibodies to malaria antigens generated by two LAIR1 insertion modalities
Creator	Lanzavecchia, Antonio Sallusto, Federica Jarrossay, David Foglierini, Mathilde Wolf, Tobias Chen, Yiwei Abdi, Abdirahman Barbieri, Sonia Bull, Peter Pieper, Kathrin Silacci-Fregni, Chiara Anderle, Marica Daubenberger, Claudia Traore, Boubacar Zenklusen, Isabelle Crompton, Peter Doumbo, Ogobara Ndungu, Francis Tran, Tuan
Source	Medline; PMC
abstract	We previously described two donors in whom the extracellular domain of LAIR1, a collagen-binding inhibitory receptor encoded on chromosome 191, was inserted between the V and the DJ segments of an antibody. This insertion generated, through somatic mutations, broadly reactive antibodies against RIFINs, a type of variant antigen expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs)2. To investigate how frequently such antibodies are produced in response to malaria infection, we screened plasma from two large cohorts of individuals living in malaria-endemic regions. We report that 5-10% of malaria-exposed individuals, but none of the European blood donors tested, have high levels of LAIR1-containing antibodies that dominate the response to IEs without conferring enhanced protection against febrile malaria. By analyzing the antibody-producing B cell clones at the protein, cDNA and gDNA level, we characterized additional LAIR1 insertions between the V and DJ segments and discovered a second insertion modality whereby the LAIR1 exon encoding the extracellular domain and flanking intronic sequences are inserted into the switch region. By exon shuffling, this mechanism leads to the production of bispecific antibodies in which the LAIR1 domain is precisely positioned at the elbow between the VH and CH1 domains. Additionally, in one donor the gDNA encoding the VH and CH1 domains was deleted, leading to the production of a camel-like LAIR1-containing antibody. Sequencing of the switch regions of memory B cells from European blood donors revealed frequent templated inserts originating from transcribed genes that, in rare cases, comprised exons with orientation and frame compatible with expression. Collectively, these results reveal different modalities of LAIR1 insertion that lead to public and dominant antibodies against IEs and suggest that insertion of templated DNA represents an additional mechanism of antibody diversification that can be selected in the immune response against pathogens and exploited for B cell engineering.
has issue date	2017-08-23(xsd:dateTime)
bibo:doi	10.1038/nature23670
bibo:pmid	28847005
has license	no-cc
sha1sum (hex)	bf73a62e8d870d8edd2bd1fb2ca68424e2e8b7d9
schema:url	https://doi.org/10.1038/nature23670
resource representing a document's title	Public antibodies to malaria antigens generated by two LAIR1 insertion modalities
has PubMed Central identifier	PMC5635981
has PubMed identifier	28847005
schema:publication	Nature
resource representing a document's body	covid:bf73a62e8d870d8edd2bd1fb2ca68424e2e8b7d9#body_text
is schema:about of	named entity 'ANTIBODIES' named entity 'expressed' named entity 'EXPRESSED' named entity 'INSERTED' named entity 'USE' named entity 'LAIR1' named entity 'ANTIBODY' named entity 'CONTENT' named entity 'CHROMOSOME' named entity 'SEGMENTS' named entity 'TEXT' named entity 'ACADEMIC' named entity 'INSERTION' named entity 'TYPE' named entity 'PREVIOUSLY' named entity 'DONORS' named entity 'REACTIVE' named entity 'COPY' named entity 'MAY VIEW' named entity 'ENCODED' named entity '191' named entity 'SURFACE' named entity '292' named entity 'COHORTS' named entity 'USERS' named entity 'INSERTION' named entity 'PRINT' named entity 'PURPOSES' named entity 'ANTIBODIES' named entity 'SUBJECT' named entity 'INHIBITORY RECEPTOR' named entity 'DATA' named entity 'RESEARCH' named entity 'INFECTION' named entity 'GENERATED' named entity 'ERYTHROCYTES' named entity 'RESPONSE TO' named entity 'LAIR1' named entity 'GENERATED' named entity 'PUBLIC' named entity 'FREQUENTLY' named entity 'LARGE' named entity 'EXTRACELLULAR DOMAIN' named entity 'INFECTED' named entity 'TO INVESTIGATE' named entity 'CONDITIONS' named entity 'DESCRIBED' named entity 'PLASMODIUM FALCIPARUM' named entity 'ANTIGEN' named entity 'MALARIA' named entity 'VARIANT' named entity 'DOCUMENTS' named entity 'PLASMA' named entity 'SOMATIC MUTATIONS' named entity 'MALARIA' named entity 'MODALITIES' named entity 'ANTIGENS' named entity 'HOW' named entity 'documents' named entity 'erythrocytes' named entity 'inserted' named entity 'response' named entity 'antibodies'

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