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Maturation-dependent expression of AIM2 in human B-cells.
Alexandra Svensson1, Marianela Patzi Churqui1,2, Kerstin Schlüter1
1Department of Rheumatology and Inflammation Research, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Plos One
|August 16, 2017
Summary
Adult B-cells express the DNA sensor Absent in Melanoma 2 (AIM2), crucial for immune responses. This protein is primarily found in memory B-cells and absent in cord blood, indicating its role in adult immunity.
Area of Science:
- Immunology
- Cell Biology
- Infectious Disease
Background:
- Intracellular DNA- and RNA-sensing receptors, like Absent in Melanoma 2 (AIM2), are vital host sensors against infections.
- AIM2's role in innate antiviral recognition is established in cell lines and animal models, but its expression in human cells is poorly understood.
Purpose of the Study:
- To investigate the expression and function of AIM2 in freshly isolated human B-cells from cord and adult peripheral blood.
- To determine AIM2 expression levels at steady state and after in vitro activation.
Main Methods:
- Analysis of AIM2 mRNA expression in different human blood cell types (cord and adult).
- Investigation of AIM2 induction by type I and type II Interferon (IFN) and poly dA:dT stimulation.
- Assessment of AIM2 expression changes upon B-cell receptor stimulation.
- Measurement of Interleukin-1 beta (IL-1β) release from adult B-cells stimulated with synthetic DNA.
Main Results:
- Adult B-cells, particularly mature memory CD27+ B-cells, expressed high levels of AIM2 mRNA at steady state, unlike cord blood B-cells.
- Both adult and cord blood B-cells upregulated AIM2 mRNA in response to type II IFN, but not type I IFN or poly dA:dT.
- B-cell receptor stimulation reduced AIM2 mRNA levels in adult B-cells.
- Adult B-cells released IL-1β upon stimulation with synthetic DNA, suggesting functional AIM2 inflammasome activation.
Conclusions:
- Functional AIM2 is preferentially expressed in adult human CD27+ B-cells.
- AIM2 expression is largely absent in cord blood mononuclear cells.
- These findings highlight a cell-type and maturation-dependent expression of AIM2 in human immunity.
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