Replicate immunosequencing as a robust probe of B cell repertoire diversity

TL;DR

This study combines flow cytometry and immunosequencing to accurately measure B cell receptor diversity, revealing insights into clone abundance and repertoire structure in human blood.

Contribution

It introduces a robust experimental design for quantifying B cell diversity, extending ecological models to immunology and providing maximum likelihood estimates.

Findings

Memory B cell repertoires show more diverse clone abundances.

Naive B cell clones mostly do not proliferate before antigen recognition.

Repertoire exhibits power law scaling in clone abundance.

Abstract

Fundamental to quantitative characterization of the B cell receptor repertoire is clonal diversity - the number of distinct somatically recombined receptors present in the repertoire and their relative abundances, defining the search space available for immune response. This study synthesizes flow cytometry and immunosequencing to study memory and naive B cells from the peripheral blood of three adults. A combinatorial experimental design was employed, constituting a sample abundance probe robust to amplification stochasticity, a crucial quantitative advance over previous sequencing studies of diversity. These data are leveraged to interrogate repertoire diversity, motivating an extension of a canonical diversity model in ecology and corpus linguistics. Maximum likelihood diversity estimates are provided for memory and naive B cell repertoires. Both evince domination by rare clones and regimes of power law scaling in abundance. Memory clones have more disparate repertoire abundances than naive clones, and most naive clones undergo no proliferation prior to antigen recognition.