V(DD)J recombination is an important and evolutionarily conserved mechanism for generating antibodies with unusually long CDR3s.

ABSTRACT: The V(DD)J recombination is currently viewed as an aberrant and inconsequential variant of the canonical V(D)J recombination. Moreover, since the classical 12/23 rule for the V(D)J recombination fails to explain the V(DD)J recombination, the molecular mechanism of tandem D-D fusions has remained unknown since they were discovered three decades ago. Revealing this mechanism is a biomedically important goal since tandem fusions contribute to broadly neutralizing antibodies with ultralong CDR3s. We reveal previously overlooked cryptic nonamers in the recombination signal sequences of human IGHD genes and demonstrate that these nonamers explain the vast majority of tandem fusions in human repertoires. We further reveal large clonal lineages formed by tandem fusions in antigen-stimulated immuno

SUBMITTER: Safonova Y 

PROVIDER: S-EPMC7605257 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature