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Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells
Götz R A Ehrhardt1, Joyce T Hsu, Lanier Gartland
1Division of Clinical and Developmental Immunology, University of Alabama at Birmingham, Birmingham, Birmingham, AL 35294, USA.
Insights
Fc receptor homologue 4 (FcRH4) marks a unique memory B cell subset. These cells are poised for immunoglobulin secretion but resist proliferation, suggesting a specialized role in immunity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Fc receptor homologue 4 (FcRH4) is a transmembrane molecule known to inhibit B cell receptor (BCR) signaling.
- Memory B cells are crucial for adaptive immunity, providing long-term protection against pathogens.
Purpose of the Study:
- To characterize the FcRH4-expressing cell population within memory B cells.
- To investigate the functional and phenotypic properties of FcRH4+ memory B cells.
Main Methods:
- Flow cytometry to identify and quantify FcRH4+ memory B cells.
- Analysis of immunoglobulin isotype switching and somatic hypermutation.
- Assessment of cell surface marker expression, including CD27, CD69, CD80, CD86, CCR1, and CCR5.
- Functional assays measuring proliferation and immunoglobulin secretion in response to various stimuli.
Main Results:
- FcRH4 expression is restricted to a distinct subpopulation of human memory B cells, many of which are CD27-negative.
- FcRH4+ memory B cells exhibit unique morphology, expressing activation markers (CD69, CD80, CD86) and chemokine receptors (CCR1, CCR5).
- These cells are primed for high-level immunoglobulin secretion upon T cell cytokine stimulation but show impaired proliferation upon BCR ligation or Staphylococcus aureus stimulation.
Conclusions:
- FcRH4 defines a unique memory B cell subset with specialized functional capabilities, including potent immunoglobulin secretion.
- The FcRH4+ memory B cell population may play a distinct role in immune responses, potentially localized to lymphoid tissues near epithelial surfaces.
- FcRH4 expression serves as a marker for a novel memory B cell subset with implications for understanding B cell differentiation and function.
Abstract:
The FcRH4 transmembrane molecule, a member of the Fc receptor homologue family, can potently inhibit B cell receptor (BCR) signaling. We show that cell surface expression of this immunoregulatory molecule is restricted to a subpopulation of memory B cells, most of which lack the classical CD27 marker for memory B cells in humans. The FcRH4+ and FcRH4- memory B cells have undergone comparable levels of immunoglobulin isotype switching and somatic hypermutation, while neither subpopulation expresses the transcription factors involved in plasma cell differentiation. The FcRH4+ memory cells are morphologically distinctive large lymphocytes that express the CD69, CD80, and CD86 cell activation markers. They are also shown to be poised to secrete high levels of immunoglobulins in response to stimulation with T cell cytokines, but they fail to proliferate in response either to BCR ligation or Staphylococcus aureus stimulation. A heightened expression of the CCR1 and CCR5 chemokine receptors may facilitate their preferential localization in lymphoid tissues near epithelial surfaces. Cell surface FcRH4 expression thus marks a unique population of memory B cells with distinctive morphology, functional capabilities, and tissue localization.
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