Regulated expression of human histocompatibility leukocyte antigen (HLA)-DO during antigen-dependent and antigen-independent phases of B cell development

• Type of Material: Article
• Authors: Xinjian Chen, Emory University; Oskar Laur, Emory University; Taku Kambayashi, Emory University; Shiyong Li, Emory University; Robert Bray, Emory University; Dominique A. Weber, Emory University; Lars Karlsson, R.W. Johnson Pharmaceutical Research Institute; Peter E. Jensen, Emory University
• Language: English
• Date: 2002-04-15
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2002, The Rockefeller University Press.
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.20012066
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 195
• Issue: 8
• Start Page: 1053
• End Page: 1062
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health (AI30554 and AI33614).
• Keywords: B cell development; HLA-DO; CD40 LIGAND; DISSOCIATION; Immunology; Life Sciences & Biomedicine; germinal center; antigen presentation; HLA-DM; GERMINAL-CENTERS; INVARIANT CHAIN PEPTIDES; Research & Experimental Medicine; CLASS-II MHC; PROCESSING MUTANT; Science & Technology; DM; HLA-DR MOLECULES; MICE; NEGATIVE SELECTION
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology; Health Sciences, Pathology

Abstract

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.