PMID- 18512810
OWN - NLM
STAT- MEDLINE
DCOM- 20080724
LR  - 20211020
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 58
IP  - 6
DP  - 2008 Jun
TI  - Direct B cell stimulation by dendritic cells in a mouse model of lupus.
PG  - 1741-50
LID - 10.1002/art.23515 [doi]
AB  - OBJECTIVE: Dendritic cells (DCs) play a major role in regulating lymphocytes, 
      including B cells, and defective DC functions have been implicated in lupus. The 
      purpose of this study was to assess the contribution of DCs to B cell 
      hyperactivity in the B6.Sle1.Sle2.Sle3 (B6.TC) murine lupus model. METHODS: We 
      compared the effects of B6 and B6.TC bone marrow-derived DCs on naive B cells 
      cocultured in the presence of lipopolysaccharide (LPS), anti-CD40, or anti-IgM. 
      We measured the proliferation, antibody production, and expression of activation 
      markers and chemokine receptors for the B cells, as well as DC cytokine 
      production. B cell proliferation was also assessed in Transwell experiments and 
      in response to activated DC supernatants or exosomes. The role of DC-produced 
      cytokines was evaluated with blocking antibodies and transgenic mice. RESULTS: 
      LPS-stimulated or anti-CD40-stimulated DCs from B6.TC mice increased B cell 
      proliferation, antibody production, and chemokine receptor expression as compared 
      with DCs from B6 mice. Cell-to-cell contact was not necessary for the augmented 
      effect of the lupus-prone DCs. Anti-CD40 treatment induced a higher production of 
      interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), IL-10, and tumor necrosis 
      factor alpha in B6.TC DCs. Blocking these individual cytokines, however, did not 
      abrogate the effects of B6.TC DCs. Additional experiments also ruled out 
      involvement of BAFF, IL-12, and interferon-alpha. CONCLUSION: Activated DCs from 
      B6.TC mice directly increase B cell effector functions. This effect depends on 
      soluble factors released by activated DCs, but none of the single major 
      DC-produced cytokines known to affect B cells are necessary. Increased sIL-6R 
      production suggests that increased sensitivity to IL-6 may be involved.
FAU - Wan, Suigui
AU  - Wan S
AD  - University of Florida, Gainesville, FL 32610-0275, USA.
FAU - Zhou, Zhenhai
AU  - Zhou Z
FAU - Duan, Biyan
AU  - Duan B
FAU - Morel, Laurence
AU  - Morel L
LA  - eng
GR  - R01 AI058150/AI/NIAID NIH HHS/United States
GR  - R01-AI-058150/AI/NIAID NIH HHS/United States
GR  - R01-AI-045050/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Antibodies/metabolism
MH  - B-Lymphocytes/*metabolism
MH  - Cell Communication/*immunology
MH  - Cell Proliferation
MH  - Coculture Techniques
MH  - Dendritic Cells/immunology/*metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Lupus Erythematosus, Systemic/*immunology
MH  - Mice
MH  - Receptors, Chemokine/metabolism
EDAT- 2008/06/03 09:00
MHDA- 2008/07/25 09:00
CRDT- 2008/06/03 09:00
PHST- 2008/06/03 09:00 [pubmed]
PHST- 2008/07/25 09:00 [medline]
PHST- 2008/06/03 09:00 [entrez]
AID - 10.1002/art.23515 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2008 Jun;58(6):1741-50. doi: 10.1002/art.23515.