Porakishvili, Nino and Memon, Azka and Vispute, Ketki and Kulikova, Nina and Clark, Edward A. and Rai, Kanti R. and Nathwani, Amit and Damle, Rajendra N. and Chiorazzi, Nicholas and Lydyard, Peter M. (2011) CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells. British Journal of Haematology, 153 (4). pp. 486-498. ISSN 0007-1048
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Official URL: http://dx.doi.org/10.1111/j.1365-2141.2011.08605.x
We previously showed that approximately 60% of B chronic lymphocytic leukaemia (B-CLL) cells express surface CD180, an orphan receptor of the Toll-like receptor family. Here we investigated the ability of anti-CD180 monoclonal antibody (mAb) to induce activation, cell cycling, survival and signalling in B-CLL cells and normal B cells. Upon addition of anti-CD180 mAb, alone or in combination with anti-CD40 mAb or recombinant IL-4 (rIL-4), expression of CD86, Ki-67, uptake of DiOC(6) , phosphorylation of signalling protein kinases and Ca(2+) flux were measured in B-CLL cells from untreated patients and normal B cells from age-matched volunteers. Normal B cells and approximately 50% of CD180(+) B-CLL clones responded to CD180 ligation by activation, cycling and increased survival comparable with, or superior to, those induced by anti-CD40 mAb or rIL-4 (Responder B-CLL). Non-responder CD180(+) B-CLL clones failed to respond to CD180 mAb and responded poorly to CD40 mAb and rIL-4. Anti-CD180 mAb induced phosphorylation of ZAP70/Syk, Erk, p38MAPK and Akt in normal B cells and Responder B-CLL cells. In contrast, Erk, p38MAPK and Akt were not phosphorylated in Non-responder B-CLL cells indicating a block in signalling and possible anergy. CD180 may provide powerful expansion and survival signals for Responder B-CLL cells and have an important prognostic value.
|Research Community:||University of Westminster > Life Sciences, School of|
|Deposited On:||31 Mar 2011 15:01|
|Last Modified:||11 Jul 2011 14:51|
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