CD62L expression marks a functionally distinct subset of memory B cells
Christopher H Hanson1, Brittany Henry1, Pradhnesh Andhare1
1Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Insights
Memory B cell subsets are distinct and regulated by specific genes. CD62L expression identifies these functionally different populations in mice and humans after SARS-CoV-2 vaccination.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Memory B cell responses involve distinct subsets with varying antigen-reactivity.
- Pathways governing memory B cell subset development and function remain largely unclear.
Purpose of the Study:
- To investigate the regulatory mechanisms of memory B cell subset differentiation.
- To identify markers that distinguish functionally distinct memory B cell subsets.
Main Methods:
- Analysis of CD62L and CD44 expression on mouse memory B cells.
- Investigating the role of Bcl6 and Zeb2 in B cell subset development.
- Examining CD62L expression on human memory B cells post-SARS-CoV-2 vaccination.
Main Results:
- CD62L and CD44 expression increases progressively on mouse memory B cells, defining distinct subsets.
- Bcl6 is crucial for memory B cell subset differentiation; its overexpression impairs CD62L+ memory B cell development.
- Bcl6 regulates genes like Bcl2 and Zeb2; Zeb2 overexpression also hinders CD62L+ memory B cell development.
- CD62L is differentially expressed on human memory B cells after SARS-CoV-2 vaccination, identifying distinct populations.
Conclusions:
- CD62L expression serves as a marker for functionally distinct memory B cell subsets.
- These findings elucidate key regulators of memory B cell subset development and function.
- CD62L's role in distinguishing memory B cell subsets is conserved across species and relevant in vaccine responses.
Abstract:
The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here, we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L+ memory B cell development. Bcl6 regulates memory B cell subset development through control of a network of genes, including Bcl2 and Zeb2. Overexpression of Zeb2 impairs the development of CD62L+ memory B cells. Importantly, CD62L is also differentially expressed on human memory B cells following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and identifies phenotypically distinct populations. Together, these data indicate that CD62L expression marks functionally distinct memory B cell subsets.
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