Phenotypic and functional characterization of human CD25+ B cells
Mikael Brisslert1, Maria Bokarewa, Pia Larsson
1Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at Gôteborg University, Gôteborg, Sweden. mikael.brisslert@rheuma.gu.se
Insights
Researchers identified a unique human B cell subset expressing the interleukin-2 receptor alpha-chain (CD25). These CD25+ B cells are potent antigen-presenting cells, bridging innate and adaptive immunity via Toll-like receptor signaling.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- B lymphocytes play crucial roles in adaptive immunity.
- Interleukin-2 receptor (IL-2R) alpha-chain, CD25, is a key component of the IL-2 receptor.
- Distinct B cell subsets with specialized functions are increasingly recognized.
Purpose of the Study:
- To identify and characterize a distinct subset of human B lymphocytes expressing CD25.
- To investigate the functional properties and regulatory mechanisms of CD25+ B cells.
- To determine the role of CD25+ B cells in immune responses.
Main Methods:
- Fluorescence-activated cell sorting (FACS) analysis to identify and quantify CD25+ B cells.
- Flow cytometry to assess cell size, granularity, and expression of other surface markers.
- In vitro stimulation assays using Toll-like receptor (TLR) ligands and Epstein-Barr virus (EBV).
- Mixed lymphocyte reactions (MLR) to evaluate antigen-presenting cell capacity.
Main Results:
- A distinct subset of circulating B cells expressing CD25 was identified, characterized by larger size and higher granularity.
- CD25 expression on B cells was selectively upregulated by TLR2, TLR4, and TLR9 ligands, mediated by the NF-kappaB pathway.
- CD25+ B cells exhibited enhanced antigen-presenting cell function and expressed higher levels of costimulatory molecules (CD27, CD80).
- Blocking CD25 on B cells significantly abrogated mixed lymphocyte reactions.
Conclusions:
- CD25+ B cells represent a phenotypically and functionally distinct B cell subset.
- These cells possess potent antigen-presenting capabilities, contributing to immune responses.
- The regulation of CD25 expression by TLRs suggests a role for CD25+ B cells in bridging innate and acquired immunity.
Abstract:
We demonstrate that humans have a phenotypically and functionally distinct subset of B lymphocytes that express the interleukin (IL)-2 receptor (IL-2R) alpha-chain, cluster of differentiation (CD) 25. We found that one-third of the circulating CD20+ B cells expressed CD25 and, using fluorescence-activated cell sorter (FACS) analysis, that these cells were significantly larger and more granulated than B cells not expressing CD25. The simultaneous expression of the other two subunits (CD122 and CD132) and the proliferative responses of cells expressing CD25 to IL-2 suggested that, in addition to CD25, functional IL-2 receptors were expressed on this cell population. CD25 expression on B cells was selectively up-regulated by Toll-like receptor 2 (TLR2), TLR4, and TLR9 ligands but not by a TLR3 ligand or Epstein-Barr virus (EBV) stimulation. Blockade of the nuclear factor (NF)-kappaB pathway completely abolished CD25 up-regulation by these B cells. Interestingly, CD25+ B cells expressed significantly higher levels of surface immunoglobulins but lacked the ability to secrete immunoglobulin (Ig), as compared with CD25- B cells. Furthermore, CD25+ B cells performed significantly better as antigen-presenting cells in allogeneic mixed lymphocyte reactions (MLR), which may be a result of their expression of high levels of the costimulatory molecules CD27 and CD80. Finally, blocking of CD25 on B cells led to an almost total abrogation of MLR. Our results indicate that CD25+ B cells have distinct phenotypic and functional properties, including the ability to contribute to antigen presentation, which is linked to their expression of CD25. Finally, the differential regulation of CD25 expression via selective TLR ligands suggests a role for CD25+ B cells in bridging innate and acquired immune responses.
