Functional interaction between CD180 Toll-like receptor (TLR) and B cell receptor (BCR) in the biology of Chronic Lymphocytic Leukaemia (CLL)
type: CreativeWork
description: Chronic Lymphocytic Leukaemia (CLL) is the most common leukaemia in the western world and remains incurable. It is driven by as yet unknown (auto)antigens via the B cell receptor (BCR) and growth, survival and expansion signals it receives from the microenvironment through a range of cytokines and receptors, including Toll-like receptors (TLR). The role of the microenvironment in the development and progression of CLL is currently of major interest. Pathogen- and damage-associated molecular patterns (PAMPs and DAMPs, respectively) represent exogenous and endogenous microenvironmental factors acting via a range of receptors, including TLR. CD180/RP105 is a membrane-associated orphan receptor of the TLR family which is expressed on various cells of the immune system including macrophages, peripheral blood monocytes, dendritic cells, naive and mature B cells and marginal zone/mantle zone B cells driving normal B-cell activation and proliferation. However, it is not expressed on germinal centre (GC) B cells. CD180 is expressed heterogeneously on CLL cells, and predominantly on CLL with mutated IGVH genes (M-CLL). Although approximately 60% of CLL clones expressed CD180, only half responded to ligation with anti-CD180 monoclonal antibody (mAb) by activation, cycling, and reduced basal apoptosis. They were termed responders (R) and CD180+ CLL samples that failed to respond to anti-CD180 mAb despite expressing a high density of CD180 receptors, were termed non-responders (NR). Our group has previously demonstrated that CD180 ligation significantly induced phosphorylation of ZAP70/Syk, ERK, p38MAPK, and AKT in R-CLL cells whilst CD180-mediated signalling in NR CLL cells did not progress downstream from ZAP70/Syk phosphorylation indicating a block in activation of downstream protein kinases, and possible anergy. However, the responses were quite heterogeneous and to further understand the CD180-mediated signalling pathways in CLL; downstream signal transduction was studied b…
abstract: Chronic Lymphocytic Leukaemia (CLL) is the most common leukaemia in the western world and remains incurable. It is driven by as yet unknown (auto)antigens via the B cell receptor (BCR) and growth, survival and expansion signals it receives from the microenvironment through a range of cytokines and receptors, including Toll-like receptors (TLR). The role of the microenvironment in the development and progression of CLL is currently of major interest. Pathogen- and damage-associated molecular patterns (PAMPs and DAMPs, respectively) represent exogenous and endogenous microenvironmental factors acting via a range of receptors, including TLR. CD180/RP105 is a membrane-associated orphan receptor of the TLR family which is expressed on various cells of the immune system including macrophages, peripheral blood monocytes, dendritic cells, naive and mature B cells and marginal zone/mantle zone B cells driving normal B-cell activation and proliferation. However, it is not expressed on germinal centre (GC) B cells. CD180 is expressed heterogeneously on CLL cells, and predominantly on CLL with mutated IGVH genes (M-CLL). Although approximately 60% of CLL clones expressed CD180, only half responded to ligation with anti-CD180 monoclonal antibody (mAb) by activation, cycling, and reduced basal apoptosis. They were termed responders (R) and CD180+ CLL samples that failed to respond to anti-CD180 mAb despite expressing a high density of CD180 receptors, were termed non-responders (NR). Our group has previously demonstrated that CD180 ligation significantly induced phosphorylation of ZAP70/Syk, ERK, p38MAPK, and AKT in R-CLL cells whilst CD180-mediated signalling in NR CLL cells did not progress downstream from ZAP70/Syk phosphorylation indicating a block in activation of downstream protein kinases, and possible anergy. However, the responses were quite heterogeneous and to further understand the CD180-mediated signalling pathways in CLL; downstream signal transduction was studied b…
author: Rajakaruna, A.
date published: 2017
date modified: 2026-07-24T06:01:47Z
provider: University of Westminster
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Westminster

PropertyValue
property ID: DOI
value: 10.34737/q254x