Shared bias in H chain V-J pairing in naive and memory B cells

INTRODUCTION: H chain rearrangement in B cells is a two-step process where first D(H) binds J(H) , and only then V(H) is joined to the complex. As such, there is no direct rearrangement between V(H) and J(H) . RESULTS: Nevertheless, we here show that the V(H) JH 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 D(H) genes or a preferred reading frame. Preferred V(H) J(H) combinations are shared between donors. DISCUSSION: These results suggest a common structural mechanism for these biases. Through development, thepreferred V(H) J(H) combinations evolve during peripheral selection to become stronger, but less shared. We propose that peripheral Heavy chain V(H) J(H) usage is initially shaped by a structural selection before the naive B cellstate, followed by pathogen-induced selection for host specific V(H) -J(H) pairs.