CD21–/low B cells in human blood are memory cells

Abstract

Summary 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 CD38–24low cells, where most of the CD38–24+ are CD27+immunoglobulin (Ig)M+IgD+ and the CD38–24low 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 CD38–24low 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.

Early B cell changes predict autoimmunity following combination immune checkpoint blockade

“…Thus, CCB therapy leads to distinct changes characterized by a decline in circulating B cells and an increase in CD21 lo B cell subsets and plasmablasts. CD21 lo B cells are a distinct B cell subset, however, their phenotype and functional properties differ in different settings (12,13). Therefore, we evaluated these cells in detail in patients with melanoma.…”

Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation

“…In addition, CD21lo cells also express elevated levels of CD11c (ITGAX) at both the transcript and protein levels (Fig 3C, 4A–B). CD11c is an integrin glycoprotein that assists cells in adhesion to the endothelium 44,45 and increased expression of CD11c has been identified in almost every non-classical memory B cell population in humans 9,10,12–16,20 . Overall, the expression profile of CD21lo cells suggests that they are less likely to re-enter GCs.…”

“…The immunological role of these different populations, as well as their relationship to other B cell subsets, remains unclear. They have largely been identified in the context of chronic infection 11,14–17,19,20 , but have also been documented in autoimmunity 13,23 , and in healthy tonsils and peripheral blood 8,9,12 . The variety of contexts in which non-classical memory B cells have been identified suggests that the memory B cell compartment is highly heterogeneous and that these non-classical cells may have distinct functional roles in humoral immunity.…”

“…Many studies have found direct evidence of this by demonstrating that these subsets have undergone isotype switching 10,11,17,20,24 and somatic hypermutation 11,17 . Additionally, non-classical memory B cells identified in chronic infection settings are enriched for antigen specific cells, which suggests they have undergone affinity maturation in GCs 10–12,17,20 .…”

Expression of Cell Adhesion Molecules and Complement Receptors in Diagnostics of Transplanted Heart Rejection

“…В ассоциации с молекулами CD19 и CD27 он обра-зует так называемый В-лимфоцитарный корецеп-торный комплекс [7]. Повышение его экспрессии напрямую связано с увеличением тяжести воспа-лительной реакции, что и наблюдалось в нашем исследовании.…”