CD21(-/low) B cells in human blood are memory cells

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.