Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO.
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.
Glazier
Kim S
KS
Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Hake
Sandra B
SB
Tobin
Helen M
HM
Chadburn
Amy
A
Schattner
Elaine J
EJ
Denzin
Lisa K
LK
D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D015536:Down-Regulation; D018858:Germinal Center / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans
D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain