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Brief Definitive Report

¹ Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
² Department of Pathology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021
³ Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021
⁴ Joan and Sanford Weill Graduate School of Medical Sciences of Cornell University Immunology Program, New York, NY 10021

Address correspondence to Lisa K. Denzin, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 509, New York, NY 10021. Phone: (212) 639-7256; Fax: (212) 717-3581. E-mail: denzinl{at}mskcc.org

Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation. Remarkably, germinal center (GC) B cells, which have low levels of DO relative to naive and memory B cells, are shown to have enhanced antigen presentation capabilities. DM protein levels also were somewhat reduced in GC B cells; however, the ratio of DM to DO in GC B cells was substantially increased, resulting in more free DM in GC B cells. We conclude that modulation of DM and DO in distinct stages of B cell differentiation represents a mechanism by which B cells regulate their capacity to function as antigen-presenting cells. Efficient antigen presentation in GC B cells would promote GC B cell–T cell interactions that are essential for B cells to survive positive selection in the GC.

Key Words: HLA-DO • HLA-DM • antigen processing • MHC class II • germinal center B cells

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