Cytidine deaminase 2 is required for <i>VLRB</i> antibody gene assembly in lampreys

Abstract

The antibodies of jawless vertebrates consist of leucine-rich repeat arrays encoded by somatically assembled <i>VLRB</i> genes. It is unknown how the incomplete germline <i>VLRB</i> loci are converted into functional antibody genes during B lymphocyte development in lampreys. In <i>Lampetra planeri</i> larvae lacking the cytidine deaminase <i>CDA2</i> gene, <i>VLRB</i> assembly fails, whereas the T lineage-associated <i>VLRA</i> and <i>VLRC</i> antigen receptor gene assemblies occur normally. Thus, <i>CDA2</i> acts in a B cell lineage-specific fashion to support the somatic diversification of <i>VLRB</i> antibody genes. CDA2 is closely related to activation-induced cytidine deaminase (AID), which is essential for the elaboration of immunoglobulin gene repertoires in jawed vertebrates. Our results thus identify a convergent mechanism of antigen receptor gene assembly and diversification that independently evolved in the two sister branches of vertebrates.