Regulated Expression of Human Histocompatibility Leukocyte Antigen (HLA)-DO During Antigen-dependent and Antigen-independent Phases of B Cell Development
| Autor: | Lars Karlsson, Robert A. Bray, Taku Kambayashi, Dominique A. Weber, Peter E. Jensen, Xinjian Chen, Oskar Laur, Shiyong Li |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Immunology Antigen presentation Naive B cell B-cell receptor Down-Regulation Bone Marrow Cells Major histocompatibility complex Monocytes Article 03 medical and health sciences 0302 clinical medicine B cell development medicine Humans Immunology and Allergy Antigen-presenting cell Cells Cultured B cell 030304 developmental biology B-Lymphocytes HLA-D Antigens 0303 health sciences HLA-DM biology HLA-DO Germinal center Cell Differentiation Dendritic Cells Germinal Center Molecular biology 3. Good health B-1 cell antigen presentation medicine.anatomical_structure biology.protein 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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