title: CD21(-/low) B cells in human blood are memory cells.
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.
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg.|Rheumatology Clinic, the Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Thorarinsdottir
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg.|Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Camponeschi
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg.
authors.forename: N
authors.initials: N
authors.lastname: Cavallini
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg.
authors.forename: O
authors.initials: O
authors.lastname: Grimsholm
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg.|Rheumatology Clinic, the Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Jacobsson
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg.|Rheumatology Clinic, the Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Gjertsson
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg.
authors.forename: I-L
authors.initials: IL
authors.lastname: Mårtensson
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D051927:CD24 Antigen / Q000276:immunology; D002454:Cell Differentiation; D005260:Female; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017464:Receptors, Complement 3d / Q000097:blood* / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D051927:CD24 Antigen; C497889:CD24 protein, human; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
keywords: B cells; CD21; TLR; memory; peripheral blood