Functionally Distinct Subpopulations of CpG-Activated Memory B Cells

Scientific Reports
|April 3, 2012
PubMed

Insights

Human B cells (Bc) differentiate into subpopulations during recall responses. Proliferating CD27(lo) Bc cells are a transient pre-plasmablast population involved in receptor editing, not alternative functions.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Human B cell (Bc) recall responses involve rapid cell division, generating diverse Bc subpopulations.
  • TLR-9 agonist CpG and cytokines activate Bc in vitro, increasing CD27 surface expression in a subset.
  • CD27 expression distinguishes Bc subpopulations with potentially different functions.

Purpose of the Study:

  • To investigate the functional roles of proliferating CD27(lo) and CD27(hi) Bc subpopulations.
  • To determine if CD27(lo) Bc cells provide alternative functions like cytokine secretion or antigen presentation.
  • To elucidate the gene regulatory networks governing Bc differentiation into CD27(lo) and CD27(hi) states.

Main Methods:

  • Genome-wide transcriptional analysis (RNA-seq) was performed.
  • CpG-activated human B cells were sorted into undivided, proliferating CD27(lo), and proliferating CD27(hi) subpopulations.
  • Transcriptome data was analyzed to identify gene expression patterns and regulatory networks.

Main Results:

  • CD27(lo) Bc cells express genes associated with B cell receptor editing, indicating a transient pre-plasmablast state.
  • CD27(hi) Bc cells are likely committed to antibody-secreting cell (ASC) differentiation.
  • Undivided Bc cells exhibit transcriptional programs for non-ASC functions, including cytokine secretion and costimulation, linking innate and adaptive immunity.

Conclusions:

  • The CD27(lo) Bc subpopulation represents a transient stage in plasmablast differentiation, primarily involved in receptor editing.
  • Undivided B cells maintain functions distinct from antibody secretion, potentially bridging innate and adaptive immune responses.
  • Gene expression patterns reveal a regulatory network governing the differentiation pathways of CD27(lo) and CD27(hi) B cells.

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