Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates.
OBJECTIVE
Differentiated dendritic cells (DC) and other antigen-presenting cells are characterized by the nuclear location of RelB, a member of the nuclear factor kappaB/Rel family. To characterize and enumerate differentiated DC in rheumatoid arthritis (RA) peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST), the expression and location of RelB were examined.


METHODS
RelB protein expression and cellular location were determined in RA PB, SF, and ST by flow cytometry and immunohistochemical analysis of purified cells or formalin-fixed tissue. DNA-binding activity of RelB was determined by electrophoretic mobility shift-Western immunoblotting assays.


RESULTS
Circulating RA PBDC resembled normal immature PBDC in that they did not express intracellular RelB protein. In RA ST serial sections, cells containing nuclear RelB (nRelB) were enriched in perivascular regions. A mean +/- SD of 84 +/- 10% of these cells were DC. The remaining nRelB+,HLA-DR+ cells comprised B cells and macrophages. Only 3% of sorted SFDC contained nRelB. However, RelB present in the nucleus of these SFDC was capable of binding DNA, and therefore capable of transcriptional activity.


CONCLUSIONS
Circulating DC precursors differentiate and express RelB after entry into rheumatoid ST. Differentiated DC can thus be identified by immunohistochemistry in formalin-fixed ST. Signals for DC maturation may differ between RA ST and SF, resulting in nuclear location of RelB predominantly in ST. This is likely to have functional consequences for the DC in these sites.
Pettit
A R
AR
University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
MacDonald
K P
KP
O'Sullivan
B
B
Thomas
R
R
D000938:Antigen-Presenting Cells / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000097:blood; D011852:Radioallergosorbent Test; D013582:Synovial Fluid / Q000737:chemistry*; D013583:Synovial Membrane / Q000737:chemistry; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000096:biosynthesis* / Q000097:blood; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; D051841:Transcription Factor RelB; D004247:DNA