Expression of relB is required for the development of thymic medulla and dendritic cells.
Dendritic cells (DC) derived from bone marrow are critical in the function of the immune system, for they are the primary antigen-presenting cells in the activation of T-lymphocyte response. Their differentiation from precursor cells has not been defined at a molecular level, but recent studies have shown an association between expression of the relB subunit of the NF-kappa B complex and the presence of DC in specific regions of normal unstimulated lymphoid tissues. Here we show that relB expression also correlates with differentiation of DC in autoimmune infiltrates in situ, and that a mutation disrupting the relB gene results in mice with impaired antigen-presenting cell function, and a syndrome of excess production of granulocytes and macrophages. Thymic UEA-1+ medullary epithelial cells from normal mice show striking similarities to DC and, interestingly, these cells are also absent in relB mutant mice. Taken together, these results suggest that relB is critical in the coordinated activation of genes necessary for the differentiation of two unrelated but phenotypically similar cells (DC and thymic UEA-1+ medullary epithelial cells) and is therefore a candidate for a gene determining lineage commitment in the immune system.
Biogen Inc., Cambridge, Massachusetts 02142.
L
L
Burkly
C
C
Hession
L
L
Ogata
C
C
Reilly
L A
LA
Marconi
D
D
Olson
R
R
Tizard
R
R
Cate
D
D
Lo
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology; D007124:Immunoenzyme Techniques; D009980:Influenza A virus / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D011518:Proto-Oncogene Proteins; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; D004247:DNA