AI-Driven BCR Modeling for Precision Immunology

Int J Mol Sci. 2026 Apr 5;27(7):3296. doi: 10.3390/ijms27073296.

Abstract

The B cell receptor (BCR) repertoire captures an individual's immunological history and antigen-driven evolution within a vast, high-dimensional sequence space. Although bulk and single-cell adaptive immune receptor repertoire sequencing (AIRR-seq) now enables deep profiling of BCR diversity, interpreting these datasets remains challenging due to strong inter-individual heterogeneity, nonlinear sequence-structure-function relationships, dynamic clonal evolution, and the rarity of functionally relevant clones. Artificial intelligence (AI) provides a conceptual and computational framework for addressing these challenges. Here, we summarize how advanced deep learning architectures, including antibody-specific language models, graph neural networks (GNNs), and generative frameworks, uncover clonal topology, structural features, and antigen-binding semantics. We further highlight applications in cancer, infectious disease, and autoimmunity. Finally, we propose a closed-loop framework that integrates multimodal datasets, interpretable AI, and iterative experimental validation to advance predictive immunology and accelerate therapeutic antibody discovery.

Keywords: BCR; antibody repertoire; deep learning; immunogenetics; machine learning.

Publication types

  • Review

MeSH terms

  • Animals
  • Artificial Intelligence*
  • Deep Learning
  • Humans
  • Neural Networks, Computer
  • Precision Medicine* / methods
  • Receptors, Antigen, B-Cell* / chemistry
  • Receptors, Antigen, B-Cell* / genetics
  • Receptors, Antigen, B-Cell* / immunology

Substances

  • Receptors, Antigen, B-Cell