title: CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells.
abstract: 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.
authors: School of Life Sciences, University of Westminster, London, UK. n.porakishvili@westminster.ac.uk
authors: Nino
authors: N
authors: Porakishvili
authors: Azka
authors: A
authors: Memon
authors: Ketki
authors: K
authors: Vispute
authors: Nina
authors: N
authors: Kulikova
authors: Edward A
authors: EA
authors: Clark
authors: Kanti R
authors: KR
authors: Rai
authors: Amit
authors: A
authors: Nathwani
authors: Rajendra N
authors: RN
authors: Damle
authors: Nicholas
authors: N
authors: Chiorazzi
authors: Peter M
authors: PM
authors: Lydyard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D004357:Drug Synergism; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D015703:Antigens, CD; C092722:CD180 protein, human; D019013:CD40 Antigens; D011994:Recombinant Proteins; D015847:Interleukin-4