Formal framework models V(D)J recombination dynamics in B-cells, suggesting insights for clonal growth viability.
This preprint introduces VDJ-KTS, a formal and probabilistic framework that models V(D)J recombination as a verifiable dynamical system rather than solely a sequence generator. The framework represents recombination as a probabilistic Kripke Transition System, enabling exact reasoning about reachability, termination, and pathological dynamical regimes under biologically grounded constraints. A central contribution is the Clonal Attractor Score (CAS), defined as the probability that recombination dynamics alone pre-configure a B-cell repertoire into a low-entropy clonal absorbing state. CAS does not model antigen-driven selection, somatic hypermutation, or microenvironmental expansion; instead, it quantifies a pre-selection susceptibility that constrains which clones can subsequently be stabilized and expanded once selection acts. All recombination parameters (segment usage, junctional insertions/deletions, retry behavior, accessibility priors) are inferred exclusively from nonproductive IGH rearrangements, ensuring that CAS reflects intrinsic recombination dynamics rather than antigenic or germinal-center selection. Productive rearrangements are used only for outcome labeling and validation. By separating recombination dynamics from downstream selection, VDJ-KTS provides a mechanistic prior on clonal sustainability and offers a formal bridge between molecular recombination mechanisms, dynamical systems theory, and clinically observed patterns of clonal dominance.
No takes yet. Share an insight, caveat, or question.
Anas Enoch (2026) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: