Introduction: H chain rearrangement in B cells is a two-step process where first DH binds JH, and only then VH is joined to the complex. As such, there is no direct rearrangement between VH and JH. Results: Nevertheless, we here show that the VHJH combinations frequency in humans deviates from the one expected based on each gene usage frequency. This bias is observed mainly in functional rearrangements, and much less in out-of-frame rearrangements. The bias cannot be explained by preferred binding for DH genes or a preferred reading frame. Preferred VHJH combinations are shared between donors. Discussion: These results suggest a common structural mechanism for these biases. Through development, thepreferred VHJH combinations evolve during peripheral selection to become stronger, but less shared. We propose that peripheral Heavy chain VHJH usage is initially shaped by a structural selection before the naive B cellstate, followed by pathogen-induced selection for host specific VH-JH pairs.
Bibliographical notePublisher Copyright:
Copyright © 2023 Levi, Dvorkin and Louzoun.
- B cells
- J genes
- V genes