Happy New Year, Blopiggers!

Just a quick one from me this time around, to draw your attention to this intriguing paper by Shi et al., published in Nature Cell Discovery late last year.

“More than one antibody of individual B cells revealed by single-cell immune profiling“
Zhan Shi, Qingyang Zhang, Huige Yan, et al.
Nature Cell Discovery (2019) 5:64

Single-cell transcriptomics (e.g. using TenX sequencing) is beginning to yield fascinating insights into the inner workings of our immune system. It has long been thought that a single B cell can only express one antibody variable domain on its surface, accounted for by theories such as allelic exclusion and isotype exclusion.

Shi et al. have detected that B cells commonly express an entirely different VH transcript to the one comprising its dominant B-Cell Receptor (5-10% of all VH transcripts). It doesn’t stop with the heavy chain either, as a whopping 60% of single B cells co-expressed Vkappa and Vlambda light chains.

This points to an entirely new mechanism of induced repertoire diversity, that individual B cells can shuffle their V, D, and J transcripts after maturation to display different cell-surface receptors. It also hints at the possibility that natural B-cells could possess bispecificity (with two entirely different BCR binding sites simultaneously engaging one or more antigens) – a realisation that would embolden pharmaceutical companies in their efforts to engineer bispecific antibody therapeutics.