title: A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus.
abstract: Human memory B cells comprise isotype-switched and nonswitched cells with both subsets displaying somatic hypermutation. In addition to somatic hypermutation, CD27 expression has also been considered a universal memory B cell marker. We describe a new population of memory B cells containing isotype-switched (IgG and IgA) and IgM-only cells and lacking expression of CD27 and IgD. These cells are present in peripheral blood and tonsils of healthy subjects and display a degree of hypermutation comparable to CD27+ nonswitched memory cells. As conventional memory cells, they proliferate in response to CpG DNA and fail to extrude rhodamine. In contrast to other recently described CD27-negative (CD27neg) memory B cells, they lack expression of FcRH4 and recirculate in the peripheral blood. Although CD27neg memory cells are relatively scarce in healthy subjects, they are substantially increased in systemic lupus erythematosus (SLE) patients in whom they frequently represent a large fraction of all memory B cells. Yet, their frequency is normal in patients with rheumatoid arthritis or chronic hepatitis C. In SLE, an increased frequency of CD27neg memory cells is significantly associated with higher disease activity index, a history of nephritis, and disease-specific autoantibodies (anti-dsDNA, anti-Smith (Sm), anti-ribonucleoprotein (RNP), and 9G4). These findings enhance our understanding of the B cell diversification pathways and provide mechanistic insight into the immunopathogenesis of SLE.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
authors.forename: Chungwen
authors.initials: C
authors.lastname: Wei
authors.forename: Jennifer
authors.initials: J
authors.lastname: Anolik
authors.forename: Amedeo
authors.initials: A
authors.lastname: Cappione
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.forename: Aimee
authors.initials: A
authors.lastname: Pugh-Bernard
authors.forename: James
authors.initials: J
authors.lastname: Brooks
authors.forename: Eun-Hyung
authors.initials: EH
authors.lastname: Lee
authors.forename: Eric C B
authors.initials: EC
authors.lastname: Milner
authors.forename: Iñaki
authors.initials: I
authors.lastname: Sanz
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007072:Immunoglobulin D; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7