Co-option of retrotransposons promotes antibody diversification.

Retrotransposons upstream of V H genes are co-opted to promote antibody diversification through L1-driven somatic hypermutation in B cells.

• Why it matters: Understanding how AID specifically targets V H genes is crucial for elucidating mechanisms of antibody diversity and affinity maturation, filling a key knowledge gap in immune biology.
• What they did: The study identified ancient, truncated L1 retrotransposons upstream of V H genes, showing that recombined V H promoters produce antisense RNAs that trigger AID recruitment via the HUSH complex, with in vivo evidence from knockout and engineered mice.
• The result: Findings reveal that old retrotransposons have physiological roles in antibody diversification and suggest B cells co-opted anti-retrotransposon silencing mechanisms, linking innate and adaptive immunity.