The Journal of Experimental Medicine
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Published 15 April 2002. doi:10.1084/jem.20012066
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© Rockefeller University Press, 0022-1007/2002/4/1053/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 8, April 15, 2002 1053-1062

Regulated Expression of Human Histocompatibility Leukocyte Antigen (HLA)-DO During Antigen-dependent and Antigen-independent Phases of B Cell Development

Xinjian Chen1, Oskar Laur1, Taku Kambayashi1, Shiyong Li1, Robert A. Bray1, Dominique A. Weber1, Lars Karlsson2 and Peter E. Jensen1

1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322
2 The R.W. Johnson Pharmaceutical Research Institute, La Jolla, CA 92037

Address correspondence to Peter E. Jensen, Department of Pathology, Emory University School of Medicine, Room 7313 WMB, 1639 Pierce Drive, Atlanta, GA 30322. Phone: 404-727-3658; Fax: 404-727-5764; E-mail: pjensen{at}emory.edu

Human histocompatibility leukocyte antigen (HLA)-DO, a lysosomal resident major histocompatibility complex class II molecule expressed in B cells, has previously been shown to be a negative regulator of HLA-DM peptide loading function. We analyze the expression of DO in human peripheral blood, lymph node, tonsil, and bone marrow to determine if DO expression is modulated in the physiological setting. B cells, but not monocytes or monocyte-derived dendritic cells, are observed to express this protein. Preclearing experiments demonstrate that ~50% of HLA-DM is bound to DO in peripheral blood B cells. HLA-DM and HLA-DR expression is demonstrated early in B cell development, beginning at the pro-B stage in adult human bone marrow. In contrast, DO expression is initiated only after B cell development is complete. In all situations, there is a striking correlation between intracellular DO expression and cell surface class II–associated invariant chain peptide expression, which suggests that DO substantially inhibits DM function in primary human B cells. We report that the expression of DO is markedly downmodulated in human germinal center B cells. Modulation of DO expression may provide a mechanism to regulate peptide loading activity and antigen presentation by B cells during the development of humoral immune responses.

Key Words: antigen presentation • B cell development • germinal center • HLA-DM • HLA-DO


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