Cytidine deaminase 2 is required for VLRB antibody gene assembly in lampreys

Sci Immunol. 2020 Mar 13;5(45):eaba0925. doi: 10.1126/sciimmunol.aba0925.

Abstract

The antibodies of jawless vertebrates consist of leucine-rich repeat arrays encoded by somatically assembled VLRB genes. It is unknown how the incomplete germline VLRB loci are converted into functional antibody genes during B lymphocyte development in lampreys. In Lampetra planeri larvae lacking the cytidine deaminase CDA2 gene, VLRB assembly fails, whereas the T lineage-associated VLRA and VLRC antigen receptor gene assemblies occur normally. Thus, CDA2 acts in a B cell lineage-specific fashion to support the somatic diversification of VLRB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Cytidine Deaminase / genetics*
  • Cytidine Deaminase / immunology
  • Cytidine Deaminase / metabolism
  • Lampreys / genetics*
  • Lampreys / immunology
  • Lampreys / metabolism
  • Receptors, Antigen / genetics*
  • Receptors, Antigen / immunology
  • Receptors, Antigen / metabolism

Substances

  • Antibodies, Monoclonal
  • Receptors, Antigen
  • Cytidine Deaminase