Journal Article

Quantitative systems pharmacology model of B cell immune response in mouse

Volkova, Alina, Helmlinger, Gabriel, Ugolkov, Yaroslav, Peskov, Kirill, Sokolov, Victor

2026

Overview

B cell-mediated immunity plays a crucial role in long-term humoral protection. However, dysregulation of B cell development and differentiation may lead to the persistence of autoreactive clones, contributing to autoimmune diseases. Despite a number of therapeutic agents in preclinical and clinical development targeting B cell biology, several challenges still limit their successful translation into clinical use. To better understand B cell-targeting mechanisms of action quantitatively and mechanistically, we developed an integrative systems pharmacology model that describes T cell-dependent B cell response to antigen exposure in mouse. The model includes 20 ordinary differential equations representing key biological processes involved in the B lymphocyte response: B cell activation in secondary lymphoid organs; antibody-secreting cell (ASC) generation; migration to the bone marrow; and redistribution to peripheral tissues. The model adequately described ASC dynamics across tissues and IgG time profiles in plasma. Local and global sensitivity analyses identified the ASC production rate as the main contributor to cell counts in the spleen and in lymph nodes, while ASC levels in the bone marrow were primarily controlled by their influx rate, reflecting survival niche availability. Moderate variations of this influx rate parameter allowed the model to capture high inter-study variability in bone marrow ASC levels, explaining the observed heterogeneity in the functional immune response. The model can be further used as a quantitative tool to study B cell responses and their dysregulation in autoimmunity. It can be extended by integrating plasma-cell biology and autoantibody production, ultimately supporting the development of new therapeutic strategies for autoimmune diseases.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Antibodies / antibody secreting cell (ASC) / Antibody-Producing Cells - immunology / Antigens / Autoantibodies / Autoimmune diseases / Autoimmunity / B cell immunity / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / Bone marrow / Cell activation / Cell differentiation / Cell-mediated immunity / Cells / Cytokines / Homeostasis / Immune response (cell-mediated) / Immune system / Immunity (Disease) / Immunoglobulin G / Immunoglobulin G - blood / Immunoglobulin G - immunology / Leukocyte migration / Literature reviews / Lymph nodes / Lymphatic system / Lymphocyte Activation - immunology / Lymphocytes / Lymphocytes B / Lymphocytes T / Mice / MIDD (model-informed drug development) / Models, Immunological / Original Research / Pathogenesis / pharmacometric modeling / Plasma / QSP model / quantitative systems pharmacology / Sensitivity analysis / Spleen / Systematic review / Systems Biology / T-Lymphocytes - immunology