Functionally Distinct Subpopulations of CpG-Activated Memory B Cells
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.
Abstract:
During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27(lo) subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27(hi) plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27(lo) and proliferating CD27(hi) subpopulations. Our data supported an alternative hypothesis, that CD27(lo) cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27(lo) and CD27(hi) Bc differentiation.
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