AUTHOR=Levi Reut , Dvorkin Shirit , Louzoun Yoram 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1166116

DOI=10.3389/fimmu.2023.1166116

ISSN=1664-3224

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