Mounting efficacious antibody responses during malarial infection has proven challenging. In Nature, Lanzavecchia and colleagues report the identification of several broadly neutralizing antibodies obtained from plasma cells isolated from several Plasmodium falciparum–infected Kenyans. Analysis of IGH sequences encoding immunoglobulin heavy-chain antibodies reveals an unexpected genetic insert from LAIR1, which encodes a collagen-binding receptor, between the variable and diversity-joining sequences encoding the antibodies. This large insert can undergo extensive somatic hypermutation in the IGH context, and these mutant LAIR1 domains are responsible for the recognition of RIFIN proteins expressed by plasmodium-infected erythocytes. It remains unclear how such insertions are generated, as they contain intron and exon sequences and both alleles of LAIR1 remain intact on chromasome 19 in both donors, which rules out the possibility of cDNA insertions or chromosomal translocations. Future studies should reveal the prevalence of this LAIR1 insertion and how it occurs, mechanistically.

Nature 529, 105–109 (2016)