Transcriptome–Proteome Analysis of Human Naive and Memory B Cell Subsets Reveals Isotype and Subclass‐Specific Phenotypes

TL;DR

This study compares gene and protein activity in different types of human B cells, revealing unique features of IgG4-switched B cells.

Contribution

The study provides a detailed molecular comparison of isotype-defined B cell subsets using combined transcriptome and proteome analysis.

Findings

IgG4-switched B cells showed the most distinct mRNA and protein expression profiles compared to naive B cells.

SDR16C5 was uniquely upregulated in IgG4-switched B cells.

Cytokine and Fc receptor expression varied among isotype-defined B cell subsets.

Abstract

Antibodies produced by B cells aid in the recognition and clearance of pathogens and are the cornerstone of vaccination strategies. Humans produce nine different antibody isotypes, and their effector functions differ according to the type of antigen and route of exposure. Phenotypic variation between isotype‐switched B cell subsets is expected but not studied in detail. To obtain a molecular definition of isotype‐defined cell identity, we performed proteomics and transcriptomics on isotype‐defined populations of human naive and memory B cells (MBCs): CD27−IgM+IgD+, CD27+CD38lo/−IgM+IgD+, CD27+CD38lo/−IgM+IgD−, and IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4 MBCs (CD27+CD38lo/−Ig+). Combined proteome and transcriptome analysis revealed that mRNA and protein expression profiles separate isotype‐defined B cell subsets according to their differentiation status. mRNA and protein expression levels correlated reasonably well for many genes. IgG4‐switched B cells were most distinct from naive B cells in terms of mRNA as well as protein expression profiles. Besides a distinct expression profile of cytokine and Fc receptors, we identified a high expression of IgE‐coding mRNA in IgG4‐switched B cells. SDR16C5 was identified as uniquely upregulated in IgG4‐switched B cells. Taken together, this study highlights the distinct phenotypic profile of IgG4‐switched B cells.

We performed combined proteome and transcriptome analysis of human isotype‐defined B cell subsets.

IgG4‐switched B cells were most distinct from naive B cells in terms of mRNA as well as protein expression profiles.

SDR16C5 was identified as uniquely upregulated in IgG4‐switched B cells.

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