Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 195, Issue 8, Pages 1053-1062Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20012066
Keywords
antigen presentation; B cell development; germinal center; HLA-DM; HLA-DO
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Funding
- NIAID NIH HHS [R37 AI033614, R21 AI030554, R01 AI030554, AI30554, AI33614, R01 AI033614] Funding Source: Medline
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Human histo compatibility 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. Precleaning experiments demonstrate that similar to50% 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.
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