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

• Published in: Journal of Immunology Vol. 178; no. 10; pp. 6624 - 6633
• Main Authors: Wei, Chungwen, Anolik, Jennifer, Cappione, Amedeo, Zheng, Bo, Pugh-Bernard, Aimee, Brooks, James, Lee, Eun-Hyung, Milner, Eric C. B, Sanz, Inaki
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-05-2007
• Subjects: Autoantibodies - biosynthesis; Autoantibodies - blood; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; Biomarkers - blood; Cell Proliferation; Female; Humans; Immunoglobulin D - biosynthesis; Immunoglobulin D - deficiency; Immunoglobulin D - genetics; Immunologic Memory - genetics; Immunophenotyping; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Male; Membrane Proteins - biosynthesis; Membrane Proteins - deficiency; Membrane Proteins - genetics; Palatine Tonsil - immunology; Palatine Tonsil - metabolism; Severity of Illness Index; Tumor Necrosis Factor Receptor Superfamily, Member 7 - biosynthesis; Tumor Necrosis Factor Receptor Superfamily, Member 7 - deficiency; Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.178.10.6624

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.