A multi-scale model for correlation in B cell VDJ usage of zebrafish

Area of Science:

• Immunology
• Computational Biology
• Systems Biology

Background:

• Zebrafish (Danio rerio) are valuable immunology models due to similarities with higher animals' adaptive immune systems.
• Understanding B cell dynamics is crucial for adaptive immunity research.

Purpose of the Study:

• To develop a multi-scale model simulating B cell dynamics in zebrafish primary and secondary immune responses.
• To explain observed correlations in VDJ gene usage within individual zebrafish B cell repertoires.

Main Methods:

• A delay ordinary differential equation (ODE) system modeled immune responses over a zebrafish's lifespan.
• A 'microscopic' random energy model (generalized NK model) determined B cell VDJ recombination distributions.
• The model calculated the probability of identical VDJ recombination between zebrafish responding to the same antigen.

Main Results:

• The generalized NK model indicated that mature B cells specific to one antigen typically utilize a single VDJ recombination.
• The probability of identical VDJ recombination (p) increases with B cell population size and selection intensity.
• Increased B cell hypermutation rate decreased the probability (p) of identical VDJ recombination.

Conclusions:

• The multi-scale model successfully predicts correlations in zebrafish immune systems, aligning with experimental findings.
• The model provides a framework for understanding VDJ recombination patterns and their impact on immune response diversity.
• This work enhances our comprehension of adaptive immunity mechanisms using zebrafish models.