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A New Population of Cells Lacking Expression of CD27 Represents a Notable Component of the B Cell Memory Compartment in Systemic Lupus Erythematosus¹

Chungwen Wei^*, Jennifer Anolik^*, Amedeo Cappione^2,*, Bo Zheng^*, Aimee Pugh-Bernard^3,*, James Brooks^4,*, Eun-Hyung Lee, Eric C. B. Milner^* and Iñaki Sanz^5,*

^* Department of Medicine, Division of Clinical Immunology and Rheumatology and Division of Pulmonary and Critical Care, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by Grants U19 Autoimmunity Center of Excellence AI56390 and R01 AI049660-01A1 (to I.S.) and National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases K08AR048303, the Lupus Foundation of America, and the Alliance for Lupus Research (to J.A.).

² Current address: Guava Technologies, Hayward, CA 94545.

³ Current address: Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical Research Center, Denver, CO 80206.

⁴ Current address: Cornell University College of Veterinary Medicine, Ithaca, New York 14853.

⁵ Address correspondence and reprint requests to Dr. Iñaki Sanz, University of Rochester School of Medicine, Box 695, 601 Elmwood Avenue, Rochester, NY 14642. E-mail address: Ignacio_Sanz{at}urmc.rochester.edu

⁶ Abbreviations used in this paper: GC, germinal center; DC, dendritic cell; SLE, systemic lupus erythematosus; DN, double negative; CD27neg, CD27 negative; RA, rheumatoid arthritis; R123, Rhodamine 123; RNP, ribonucleoprotein.

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