Expression profile of FcγRIIb on leukocytes and its dysregulation in systemic lupus erythematosus

Kaihong Su, Hengxuan Yang, Xinrui Li, Xiaoli Li, Andrew W. Gibson, John M. Cafardi, Tong Zhou, Jeffrey C. Edberg, Robert P. Kimberly

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

FcγRIIb (CD32B, Online Mendelian Inheritance in Man 604590), an IgG FcR with a tyrosine-based inhibitory motif, plays a critical role in the balance of tolerance and autoimmunnity in murine models. However, the high degree of homology between FcγRIIb and FcγRIIa in humans and the lack of specific Abs to differentiate them have hampered study of the normal expression profile of FcγRIIb and its potential dysregulation in autoimmune diseases such as systemic lupus erythematosus (SLE). Using our newly developed anti-FcγRIIb mAb 4F5 which does not react with FcγRIIa, we found that FcγRIIb is expressed on the cell surface of circulating B lymphocytes, monocytes, neutrophils, myeloid dendritic cells (DCs), and at very low levels on plasmacytoid DCs from some donors. Normal donors with the less frequent 2B.4 promoter haplotype have higher FcγRIIb expression on monocytes, neutrophils, and myeloid DCs similar to that reported for B lymphocytes, indicating that FcγRIIb expression on both myeloid and lymphoid cells is regulated by the naturally occurring regulatory single nucleotide polymorphisms in the FCGR2B promoter. FcγRIIb expression in normal controls is up-regulated on memory B lymphocytes compared with naive B lymphocytes. In contrast, in active SLE, FcγRIIb is significantly down-regulated on both memory and plasma B lymphocytes compared with naive and memory/plasma B lymphocytes from normals. Similar down-regulation of FcγRIIb on myeloid-lineage cells in SLE was not seen. Our studies demonstrate the constitutive regulation of FcγRIIb by natural gene polymorphisms and the acquired dysregulation in SLE autoimmunity, which may identify opportunities for using this receptor as a therapeutic target.

Original languageEnglish (US)
Pages (from-to)3272-3280
Number of pages9
JournalJournal of Immunology
Volume178
Issue number5
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Su, K., Yang, H., Li, X., Li, X., Gibson, A. W., Cafardi, J. M., Zhou, T., Edberg, J. C., & Kimberly, R. P. (2007). Expression profile of FcγRIIb on leukocytes and its dysregulation in systemic lupus erythematosus. Journal of Immunology, 178(5), 3272-3280. https://doi.org/10.4049/jimmunol.178.5.3272