CD21(-/low) B cells in human blood are memory cells
K Thorarinsdottir1,2, A Camponeschi1,3, N Cavallini1
1Department of Rheumatology and Inflammation Research, University of Gothenburg.
Insights
CD21-low B cells, found in healthy adults, are identified as memory B cells. These cells, distinct from naive B cells, exhibit unique characteristics and respond to stimulation, suggesting a role in immune memory.
Area of Science:
- Immunology
- Cell Biology
Background:
- Complement receptor 2 (CR2, CD21) acts as a B cell co-receptor, lowering the threshold for B cell activation.
- Low or absent surface CD21 (CD21(-/low)) B cells are elevated in chronic inflammatory and autoimmune conditions.
- The CD21(-/low) B cell subset in healthy individuals remains poorly characterized.
Purpose of the Study:
- To characterize the CD21(-/low) B cell subset in peripheral blood of healthy adults.
- To investigate the functional capacity and phenotype of CD21(-/low) B cells.
- To determine if CD21(-/low) B cells represent a distinct memory B cell population.
Main Methods:
- Flow cytometry analysis of peripheral blood B cells to identify and quantify CD21(-/low) populations.
- Phenotypic characterization using markers such as CD38, CD24, CD27, IgM, IgD, CD95, and CD62L.
- Functional assays involving stimulation via B cell receptor (BCR), Toll-like receptor (TLR)-7/8, and interleukin (IL)-2 to assess proliferation and differentiation.
Main Results:
- CD21(-/low) B cells constitute approximately 5% of adult peripheral blood B cells and are rare in cord blood.
- This subset comprises CD38(-) CD24(+) (mostly naive-like IgM+IgD+) and CD38(-) CD24(low) (switched) cells.
- CD21(-/low) cells exhibit memory B cell-like expression of CD95 and CD62L and largely lack ABCB1 transporter expression.
- Upon stimulation, CD21(-/low) B cells proliferate and differentiate comparably to classical memory B cells, though the switched subset requires BCR co-stimulation for optimal response.
Conclusions:
- CD21(-/low) B cells in healthy donors represent a distinct memory B cell population.
- These cells possess unique phenotypic and functional characteristics differentiating them from naive B cells.
- The findings suggest that certain memory B cell subsets rely on both TLR and BCR signaling for activation.
Abstract:
The complement receptor 2 (CR2, CD21) is part of a complex (CD21/CD19/CD81) acting as a co-receptor to the B cell receptor (BCR). Simultaneous triggering of the BCR and CD21 lowers the threshold for B cell activation. Although CD21 is important, B cells that express low amounts or lack surface CD21 (CD21(-/low) ) are increased in conditions with chronic inflammation, e.g. autoimmune diseases. However, little is known about the CD21(-/low) B cell subset in peripheral blood from healthy donors. Here, we show that CD21(-/low) cells represent approximately 5% of B cells in peripheral blood from adults but are barely detectable in cord blood, after excluding transitional B cells. The CD21(-/low) subset can be divided into CD38(-) 24(+) and CD38(-) 24(low) cells, where most of the CD38(-) 24(+) are CD27(+) immunoglobulin (Ig)M(+) IgD(+) and the CD38(-) 24(low) are switched CD27(-) . Expression levels of additional markers, e.g. CD95 and CD62L, are similar to those on classical memory B cells. In contrast to naive cells, the majority of CD21(-/low) cells lack expression of the ABCB1 transporter. Stimulation with a combination of BCR, Toll-like receptor (TLR)-7/8 and interleukin (IL)-2 induces proliferation and differentiation of the CD21(-/low) B cells comparable to CD21(+) CD27(+) memory B cells. The response excluding BCR agonist is not on par with that of classical memory B cells, although clearly above that of naive B cells. This is ascribed to a weaker response by the CD38(-) 24(low) subset, implying that some memory B cells require not only TLR but also BCR triggering. We conclude that the CD21(-/low) cells in healthy donors are memory B cells.
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