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Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

Published on: April 20, 2021

Position-Dependent Differential Targeting of Somatic Hypermutation.

Julian Q Zhou¹, Steven H Kleinstein^2,3

¹Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511; and.

Journal of Immunology (Baltimore, Md. : 1950)

|November 14, 2020

Summary

Somatic hypermutation (SHM) targeting within immunoglobulin (Ig) sequences is position-dependent, not uniform across motifs. This finding challenges existing computational models and highlights the importance of sequence context in SHM.

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Area of Science:

Immunology
Genetics
Computational Biology

Background:

Somatic hypermutation (SHM) is crucial for antibody diversity and humoral immunity.
SHM targeting of immunoglobulin (Ig) sequences exhibits known biases.
Current computational models often assume uniform motif targeting, irrespective of nucleotide position.

Purpose of the Study:

To investigate whether DNA motif targeting by SHM is position-dependent within Ig sequences in vivo.
To challenge the assumption of uniform SHM targeting in computational modeling.

Main Methods:

Analysis of 956,157 human Ig sequences.
Controlling for the influence of selection.
Examining position-dependent SHM targeting across various motifs and their alleles.

Main Results:

SHM targeting likelihood varies significantly with motif position within Ig sequences.
Position-dependent targeting was observed for approximately three-quarters of unique motifs analyzed.
SHM targeting correlated positively with the mutability of the surrounding sequence neighborhood.

Conclusions:

The assumption of uniform SHM motif targeting is invalid in vivo.
SHM targeting is influenced by sequence context and position, not just motif identity.
Findings necessitate refinement of computational models for SHM targeting.