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

Reut Levi; Shirit Dvorkin; Yoram Louzoun

doi:10.3389/fimmu.2023.1166116

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

Reut Levi, Shirit Dvorkin, Yoram Louzoun

Research output: Contribution to journal › Article › peer-review

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_HJ_H combinations are shared between donors. Discussion: These results suggest a common structural mechanism for these biases. Through development, thepreferred V_HJ_H combinations evolve during peripheral selection to become stronger, but less shared. We propose that peripheral Heavy chain V_HJ_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.

Original language	English
Article number	1166116
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1166116
State	Published - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Levi, Dvorkin and Louzoun.

Funding

The work of YL and RL was funded by grants ISF 870/20 as well as by an Israel MOH grant on preventive medicine and a Vatat DSI grant. Acknowledgments The authors thank Wenzhao Meng, Aaron M. Rosenfeld and Eline T. Luning Prak for sharing processed data from spleen samples of human organ donors that were generated under the auspices of the NIH-funded Human Pancreas Analysis Program (HPAP, (), NIH grant number U01 DK112217). IgH sequencing on HPAP samples was performed in the Human Immunology Core at the University of Pennsylvania, which is supported in part by NIH P30 AI045008 and P30 CA016520. We also wish to thank Miriam Beller for the English editing.

Funders	Funder number
Vatat DSI
National Institutes of Health	P30 CA016520, U01 DK112217, P30 AI045008

Keywords

B cells
J genes
V genes
rearragement
selection
structural

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10.3389/fimmu.2023.1166116

Cite this

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title = "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 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.",

keywords = "B cells, J genes, V genes, rearragement, selection, structural",

author = "Reut Levi and Shirit Dvorkin and Yoram Louzoun",

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year = "2023",

doi = "10.3389/fimmu.2023.1166116",

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AU - Levi, Reut

AU - Dvorkin, Shirit

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N2 - 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.

AB - 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.

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KW - J genes

KW - V genes

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

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Keywords

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