Disease relevance of CD180

• Expression of CD180, a toll-like receptor homologue, is up-regulated in children with Kawasaki disease [1].
• The percentages of CD180 positive B cells were significantly higher in children with KD or viral infections than in those with bacterial infections or in healthy controls [1].
• In addition, there was an increased frequency of RP105-negative B-lymphocytes in the peripheral blood in several rheumatic diseases, such as systemic lupus erythematosus, suggesting the involvement of RP105 in the pathophysiology of autoimmunity [2].
• They are associated with small molecules called MD-2 and MD-1, respectively, to form heterodimers (TLR4/MD-2 and RP105/MD-1) and function as recognition/signaling molecules of lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria [2].
• Further analysis of the structure and function of TLR4/MD-2 and RP105/MD-1 will provide a better understanding of the pathophysiology, and a chance to develop evidence-based treatments for septic shock syndrome and autoimmunity [2].

High impact information on CD180

• RP105 is a B-cell surface molecule that has been recently assigned as CD180 [3].
• RP105 is associated with MD-1 and transmits an activation signal in human B cells [4].
• The B-cell activation pathway using RP105 is conserved in humans [4].
• Moreover, the anti-RP105 MoAb activates B cells, leading to increases in cell size, expression of a costimulatory molecule CD80, and DNA synthesis [4].
• MD-1 is anchored by radioprotective 105 (RP105), and MD-2 is associated with TLR4 [5].

Biological context of CD180

• The human LY64 locus was localized to 5q12 by fluorescence in situ hybridization, confirming the syntenic relationship between these regions of the mouse and human chromosomes [6].
• These results suggest that similar mechanisms may be involved in the up-regulation of B cell CD180 expression in patients with either KD or viral infections [1].
• We identified a human RP105 homolog and mapped the gene to chromosome 5q12.3-13 [7].

Anatomical context of CD180

• Analysis of transfectant cell lines and gene-targeted mice revealed that both MD-2 and MD-1 are involved in the recognition of LPS as well as in the regulation of intracellular distribution and the surface expression of TLR4 and RP105, respectively [2].
• Further, RP105 is not B-cell-specific; its expression directly mirrors that of TLR-4 on dendritic cells and macrophages [8].
• For the assay of autoantibodies, RP105-positive and RP105-negative B cells were cultured separately for 10 days with anti-CD3 antibody-stimulated T cells [9].
• While previous studies have shown that RP105 is expressed on surface IgM+IgD+2 B cells in mice, human RP105 was shown to be expressed on all subsets of mature B cells and dendritic cells [10].

Associations of CD180 with chemical compounds

• Role of TLR4/MD-2 and RP105/MD-1 in innate recognition of lipopolysaccharide [2].

Regulatory relationships of CD180

• Separate studies of a Radioprotective 105 (RP105) and MD-1 heterodimer expressed by cells led to the identification of MD-2 as a molecule associated with TLR4 [11].
• SAC and IL-6 enhanced production of IgG and IgM by RP105-negative B cells but failed to induce such production by RP105-positive B cells [9].

Other interactions of CD180

• Ten human TLRs have been cloned as well as RP105, a protein similar to TLR4 but lacking the intracellular signaling domain [12].
• To identify potential sites of action, we used quantitative real-time RT-PCR to examine systematically the expression of mRNAs encoding all known human TLRs, RP105, and several other proteins important in TLR functions (e.g., MD-1, MD-2, CD14, MyD88) [12].
• Little or no TLR5 and RP105 mRNA expression was observed in HUVEC, whereas a moderate level was detected in PBMC and THP-1 cells [13].
• Inhibition of TLR-4/MD-2 signaling by RP105/MD-1 [8].
• METHODS: RP105-positive and RP105-negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin-6 (IL-6) [9].

Analytical, diagnostic and therapeutic context of CD180

• Molecular cloning of a human RP105 homologue and chromosomal localization of the mouse and human RP105 genes (Ly64 and LY64) [6].
• Western blot analysis demonstrates specific expression of human RP105 in human B lymphocytes [7].
• Bronchoalveolar lavage fluid from a patient with DM and active interstitial pneumonitis contained a large number of RP105 negative B cells [14].
• METHODS: The population of RP105 negative B cells (activated B cells) in the peripheral blood mononuclear cells of seven patients with dermatomyositis (DM) and 11 with polymyositis (PM) was analysed by flow cytometry [14].

References