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Updated: Mar 13, 2026

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Transcriptome-Proteome Analysis of Human Naive and Memory B Cell Subsets Reveals Isotype and Subclass-Specific

Jana Koers1, Arie J Hoogendijk1, Simon Tol1

  • 1Sanquin Research, and Landsteiner Laboratory, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

European Journal of Immunology
|March 12, 2026
PubMed
Summary

Human B cells produce nine antibody isotypes, crucial for immunity and vaccines. This study reveals unique molecular profiles for IgG4-switched B cells, distinguishing them from other B cell types.

Keywords:
B cellsIgG4Isotypesproteomicstranscriptomics

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • B cells produce diverse antibody isotypes essential for pathogen defense and vaccination.
  • While effector functions vary by isotype, detailed molecular differences between isotype-defined B cell subsets remain understudied.
  • Understanding these differences is key to comprehending adaptive immunity.

Purpose of the Study:

  • To define the molecular identity of human isotype-defined B cell subsets.
  • To investigate phenotypic variations among naive and memory B cells (MBCs) based on their antibody isotype.
  • To identify unique molecular markers distinguishing these subsets.

Main Methods:

  • Proteomics and transcriptomics were performed on carefully isolated human naive and memory B cell populations.
  • Isotype-defined populations included naive B cells and MBCs expressing IgM, IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4.
  • Integrated analysis of mRNA and protein expression data was conducted.

Main Results:

  • Proteome and transcriptome analyses revealed distinct molecular profiles for isotype-defined B cell subsets, correlating with differentiation status.
  • IgG4-switched B cells exhibited the most distinct mRNA and protein expression profiles compared to naive B cells.
  • IgG4-switched B cells showed unique expression of cytokine and Fc receptors, high IgE-coding mRNA, and upregulation of SDR16C5.

Conclusions:

  • This study provides a molecular definition for isotype-defined human B cell subsets.
  • IgG4-switched B cells possess a unique phenotypic profile, setting them apart from other B cell populations.
  • The findings contribute to a deeper understanding of B cell heterogeneity and function in human immunity.