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

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.

CD21 -/low B cells: A Snapshot of a Unique B Cell Subset in Health and Disease.

B cells represent one of the cellular components of the immune system that protects the individual from invading pathogens. In response to the invader, these cells differentiate into plasma cells and produce large amounts of antibodies that bind to and eliminate the pathogen. A hallmark of autoimmune diseases is the production of autoantibodies i.e. antibodies that recognize self. Those that are considered pathogenic can damage tissues and organs, either by direct binding or when deposited as immune complexes. For decades, B cells have been considered to play a major role in autoimmune diseases by antibody production. However, as pathogenic autoantibodies appear to derive mainly from T cell dependent responses, T cells have been the focus for many years. The successful treatment of patients with autoimmune diseases with either B cell depletion therapy (rituximab) or inhibition of B cell survival (belimumab), suggested that not only the autoantibodies but also other B cell features are important. This has caused a surge of interest in B cells and their biology resulting in the identification of various subsets e.g. regulatory B cells, several memory B cell subsets etc. Also, in other conditions such as chronic viral infections and primary immunodeficiency, several B cell subsets with unique characteristics have been identified. In this review, we will discuss one of these subsets, a subset that is expanded in conditions characterized by chronic immune stimulation. This B cell subset lacks, or expresses low, surface levels of the complement receptor 2 (CD21) and has therefore been termed CD21(-/low) B cells.