CD83 regulates splenic B cell maturation and peripheral B cell homeostasis.
The central function of murine CD83 that is expressed on thymic epithelial cells is to induce the progression of double-positive thymocytes to single CD4-positive T cells. Several lines of evidence suggest an additional role for CD83 in the regulation of peripheral T and B cell responses. Here we show that CD83 is expressed by immature B cells and regulates their further maturation and survival in the periphery. Employing mixed bone marrow chimeras, we compare wild-type, CD83 over-expressing and CD83-deficient B cells within the same host. CD83 over-expression on the immature B cells themselves led to an accumulation of transitional B cells and a reciprocally reduced maturation of follicular B cells that was strictly correlated to the intensity of CD83 over-expression. The absence of CD83 on B cells resulted in a decreased maturation of marginal zone B cells and conferred a mild selection advantage for B cell survival in the periphery. Consenting with these findings, the over-expression of CD83 specifically and dose dependently interfered with homeostasis of B cells while T cell survival was not affected by CD83 over-expression over a period of 30 weeks. Taken together, our data suggest that CD83 negatively regulates B cell maturation and survival.
Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany.
Katja
K
Lüthje
Birte
B
Kretschmer
Bernhard
B
Fleischer
Minka
M
Breloer
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D025461:Feedback, Physiological / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen