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CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells
Author(s) -
Porakishvili Nino,
Memon Azka,
Vispute Ketki,
Kulikova Nina,
Clark Edward A.,
Rai Kanti R.,
Nathwani Amit,
Damle Rajendra N.,
Chiorazzi Nicholas,
Lydyard Peter M.
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08605.x
Subject(s) - cd40 , chronic lymphocytic leukemia , cd86 , mapk/erk pathway , protein kinase b , syk , cd19 , zap70 , cancer research , phosphorylation , monoclonal antibody , b cell , cd5 , microbiology and biotechnology , biology , medicine , immunology , antibody , receptor , t cell , leukemia , antigen presenting cell , tyrosine kinase , immune system , in vitro , biochemistry , cytotoxic t cell
Summary 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.