A data-driven model for somatic hypermutation of B-cell*

B cells are a crucial player in the adaptive immune system as antibodies of high affinity are essential to swiftly eradicate pathogens. A specific response is made possible by processes of recombination and subsequent mutation of the immunoglobulin-coding genes that ensure an extraordinary diversity of the B cell repertoire. Thanks to hypermutations, affinity maturation converges promptly to deliver antibodies of desired specificity. We use high-throughput repertoire sequencing data to reconstruct B cell lineages from non-productive sequences and model the inherent biases of the mutation process. We describe preferential targeting of motifs and regions along the sequence and observe that mutations occurring concomitantly along B-cell lineages tend to co-localise, suggesting a possible mechanism for accelerating affinity maturation

Reference:
Natanael Spisak, Aleksandra M Walczak, Thierry Mora, Learning the heterogeneous hypermutation landscape of immunoglobulins from high-throughput repertoire data, Nucleic Acids Research, gkaa825, doi.org/10.1093/nar/gkaa825