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

Abstract

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_HJH 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.

Keywords: B cells; J genes; V genes; rearragement; selection; structural.