Direct B cell stimulation by dendritic cells in a mouse model of lupus

✍ Scribed by Suigui Wan; Zhenhai Zhou; Biyan Duan; Laurence Morel

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 420 KB
• Volume: 58
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.23515

✦ Synopsis

Abstract

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 α 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‐α.

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.