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Isolation of Precursor B-cell Subsets from Umbilical Cord Blood

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Delineating Human B Cell Precursor Development With Genetically Identified PID Cases as a Model.

Marjolein W J Wentink¹, Tomas Kalina², Martin Perez-Andres³

¹Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.

Frontiers in Immunology

|December 19, 2019

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B-cell development in human bone marrow is a complex, non-linear process involving parallel pathways. Precursor B-cells differentiate asynchronously, influenced by V(D)J recombination and pre-B-cell receptor signaling.

Area of Science:

Immunology
Hematology
Cell Biology

Background:

B-cell precursors (BCP) develop in bone marrow (BM) from hematopoietic stem cells.
Normal B-cell development involves sequential immunoglobulin gene rearrangement and signaling via pre-B-cell receptor (pre-BCR) and B-cell receptor (BCR) complexes.
Understanding BCP differentiation is crucial for identifying developmental defects.

Purpose of the Study:

To investigate normal immunophenotypic changes during human BCP differentiation in BM.
To analyze the impact of genetic defects in V(D)J recombination or pre-BCR signaling on BCP development.
To elucidate the linearity and synchronicity of BCP differentiation pathways.

Main Methods:

Utilized a 10-color antibody panel for flow cytometry analysis of human BM samples.

Keywords:

bone marrow flow cytometry immunoglobulin repertoire next generation sequence (NGS)precursor B-cell

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Last Updated: Jan 1, 2026

Isolation of Precursor B-cell Subsets from Umbilical Cord Blood

Isolation of Precursor B-cell Subsets from Umbilical Cord Blood

Published on: April 16, 2013

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Published on: January 20, 2019

Flow Cytometric Characterization of Murine B Cell Development

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Published on: January 22, 2021

Studied BCP subsets from healthy controls and patients with specific genetic defects.

Employed Next Generation Sequencing (NGS) to analyze immunoglobulin heavy chain (IGH) gene rearrangements.

Main Results:

Observed heterogeneous BCP phenotypes and asynchronous marker expression, particularly at preB-I and preB-II stages.
NGS revealed diverse IGH gene rearrangement statuses, indicating non-linear differentiation.
Identified complex, parallel BCP maturation pathways rather than a single linear progression.

Conclusions:

Human B-cell development in BM is a complex network of parallel pathways, not a linear process.
Differentiation is asynchronous, with BCP transitioning as a continuum influenced by V(D)J recombination checkpoints.
Pre-BCR and BCR signaling play critical roles in guiding BCP production and selection.