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CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells

Nino Porakishvili1, Azka Memon, Ketki Vispute

  • 1School of Life Sciences, University of Westminster, London, UK. n.porakishvili@westminster.ac.uk

British Journal of Haematology
|March 30, 2011
PubMed

Insights

Anti-CD180 monoclonal antibody activates normal B cells and some B chronic lymphocytic leukaemia (B-CLL) cells, promoting their survival and cell cycling. Non-responder B-CLL cells show signaling defects, suggesting CD180

Area of Science:

  • Immunology
  • Hematology
  • Cell Biology

Background:

  • B chronic lymphocytic leukaemia (B-CLL) cells express CD180, an orphan receptor in the Toll-like receptor family.
  • The functional role of CD180 in B-CLL and normal B cells remains largely unexplored.

Purpose of the Study:

  • To investigate the effects of anti-CD180 monoclonal antibody (mAb) on B-CLL and normal B cell activation, cell cycling, survival, and intracellular signaling.
  • To determine if CD180 ligation can induce responses in B-CLL cells and identify potential prognostic value.

Main Methods:

  • B-CLL cells from untreated patients and normal B cells were treated with anti-CD180 mAb, alone or with anti-CD40 mAb or recombinant IL-4 (rIL-4).
  • Expression of CD86 and Ki-67, DiOC(6) uptake, Ca(2+) flux, and protein kinase phosphorylation (ZAP70/Syk, Erk, p38MAPK, Akt) were measured.

Main Results:

  • Normal B cells and approximately 50% of CD180(+) B-CLL cells (Responder B-CLL) responded to anti-CD180 mAb with activation, cycling, and increased survival.
  • Non-responder CD180(+) B-CLL clones showed poor responses to anti-CD180 mAb, anti-CD40 mAb, and rIL-4, indicating signaling pathway defects.
  • Anti-CD180 mAb induced phosphorylation of key signaling molecules in Responder B-CLL and normal B cells, but not in Non-responder B-CLL cells.

Conclusions:

  • CD180 ligation can provide potent survival and expansion signals for Responder B-CLL cells.
  • Non-responder B-CLL cells exhibit signaling anergy, suggesting CD180 status may have prognostic implications in B-CLL.
  • Targeting CD180 could be a potential therapeutic strategy for specific B-CLL patient subsets.

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