Nature newly published a research on August 23th that the scientists discovered that additional LAIR1 insertions, as a new insertion modality, would lead to the production of bispecific antibodies against infected erythrocytes of malaria.
Leukocyte-associated immunoglobulin-like receptor (LAIR1) is a collagen-binding inhibitory receptor encoded on chromosome 19. In previously studies, the scientists inserted the extracellular domain of LAIR1 between the V and DJ segments of an antibody. The antibodies are generated from a single expanded B-cell clone and through the distinct somatic mutations in the LAIR1 domain, could obtain broadly reactive antibodies against RIFINs. As a type of variant antigen expressed on the surface of Plasmodium falciparum-infected erythrocytes, RIFIN provides the pathogen with abundance and variability to escape from host antibodies. Hence, it is the important targets of naturally acquired immunity against malaria.
To further investigate how frequently such antibodies were produced in response to malaria infection, researchers tested the plasma from two groups of individuals who lived in malaria-endemic regions. They found that that 5–10% of malaria-exposed individuals, except for the European-blood individuals, had high levels of LAIR1-containing antibodies which were acted essentially on infected erythrocytes in febrile malaria, especially characterized additional LAIR1 insertions between the V and DJ segments. By analyzing the antibody-producing B cell clones at the protein level, a second insertion modality which the LAIR1 exon and flanking intronic sequences are inserted into the switch region was discovered. The LAIR1 domain was precisely positioned at the elbow between the VH and CH1 domains by exon shuffling. Otherwise, deletion of the genomic DNA encoding the VH and CH1 domains would generate a camel-like LAIR1-containing antibody. Furthermore, frequent templated inserts from transcribed genes might comprise exons with orientations and frames compatible with expression in rare cases.
The article revealed the antibodies from different modalities of LAIR1 insertion, could provide a protection against infected erythrocytes, and also indicated that insertion of templated DNA increased antibody diversification in the immune response against pathogens and exploited for B cell engineering.
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