Functional antibodies exhibit light chain coherence

David B. Jaffe (), Payam Shahi, Bruce A. Adams, Ashley M. Chrisman, Peter M. Finnegan, Nandhini Raman, Ariel E. Royall, FuNien Tsai, Thomas Vollbrecht, Daniel S. Reyes, N. Lance Hepler and Wyatt J. McDonnell ()
Additional contact information
David B. Jaffe: 10x Genomics
Payam Shahi: 10x Genomics
Bruce A. Adams: 10x Genomics
Ashley M. Chrisman: 10x Genomics
Peter M. Finnegan: 10x Genomics
Nandhini Raman: 10x Genomics
Ariel E. Royall: 10x Genomics
FuNien Tsai: 10x Genomics
Thomas Vollbrecht: 10x Genomics
Daniel S. Reyes: 10x Genomics
Wyatt J. McDonnell: 10x Genomics

Nature, 2022, vol. 611, issue 7935, 352-357

Abstract: Abstract The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies that bind particular antigens1. In most mammals, antibodies are composed of heavy and light chains that are generated sequentially by recombination of V, D (for heavy chains), J and C gene segments. Each chain contains three complementarity-determining regions (CDR1–CDR3), which contribute to antigen specificity. Certain heavy and light chains are preferred for particular antigens2–22. Here we consider pairs of B cells that share the same heavy chain V gene and CDRH3 amino acid sequence and were isolated from different donors, also known as public clonotypes23,24. We show that for naive antibodies (those not yet adapted to antigens), the probability that they use the same light chain V gene is around 10%, whereas for memory (functional) antibodies, it is around 80%, even if only one cell per clonotype is used. This property of functional antibodies is a phenomenon that we call light chain coherence. We also observe this phenomenon when similar heavy chains recur within a donor. Thus, although naive antibodies seem to recur by chance, the recurrence of functional antibodies reveals surprising constraint and determinism in the processes of V(D)J recombination and immune selection. For most functional antibodies, the heavy chain determines the light chain.

Date: 2022
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DOI: 10.1038/s41586-022-05371-z

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