A Multi-Scale Model for Correlation in B Cell VDJ Usage of Zebrafish

TL;DR

This paper presents a multi-scale model of zebrafish B cell immune responses that explains VDJ usage correlations, integrating differential equations and a microscopic energy model to predict immune repertoire similarities.

Contribution

It introduces a novel multi-scale modeling approach combining delay differential equations and a microscopic energy model to analyze B cell VDJ usage correlations in zebrafish.

Findings

Model accurately predicts VDJ usage correlations observed experimentally.

Probability of shared VDJ recombination increases with B cell population size.

Hypermutation rate inversely affects VDJ sharing probability.

Abstract

The zebrafish (\emph{Danio rerio}) is one of the model animals for study of immunology because the dynamics in the adaptive immune system of zebrafish are similar to that in higher animals. In this work, we built a multi-scale model to simulate the dynamics of B cells in the primary and secondary immune responses of zebrafish. We use this model to explain the reported correlation between VDJ usage of B cell repertoires in individual zebrafish. We use a delay ordinary differential equation (ODE) system to model the immune responses in the 6-month lifespan of a zebrafish. This mean field theory gives the number of high affinity B cells as a function of time during an infection. The sequences of those B cells are then taken from a distribution calculated by a "microscopic" random energy model. This generalized $NK$ model shows that mature B cells specific to one antigen largely possess a single VDJ recombination. The model allows first-principles calculation of the probability, $p$, that two zebrafish responding to the same antigen will select the same VDJ recombination. This probability $p$ increases with the B cell population size and the B cell selection intensity. The probability $p$ decreases with the B cell hypermutation rate. The multi-scale model predicts correlations in the immune system of the zebrafish that are highly similar to that from experiment.