Disease relevance of CD72

• Plasma cell differentiation and Ig syntheses were diminished by CD72 ligation in the presence of Staphylococcus aureus Cowan strain (SAC) plus IL-2 but not in the presence of CD40 signaling or CpG oligodeoxynucleotide [1].
• CD5 and/or CD72 engagement delivers critical costimulatory signals in B-1a, B-2, and B cells from patients with chronic lymphocytic leukemia, but with different requirements and patterns [2].
• Increased expression of the B-cell-regulatory molecule CD72 in primary Sjögren's syndrome [3].
• Therefore, CD72 may become an important marker for progenitor B-cell leukemias [4].
• Human Lyb-2 mRNA is expressed in normal human tonsils and bone marrow cells, in the pre-B cell line REH, in three Burkitt lymphoma cell lines, and in some EBV-transformed B cell lines, but not in antibody-secreting myeloma cell lines, T cell lines, or a promyelocytic leukemia cell line [5].

High impact information on CD72

• The B-cell surface protein CD72/Lyb-2 is the ligand for CD5 [6].
• Expression cloning revealed that the CD100 receptor on lymphocytes is CD72, a negative regulator of B cell responsiveness [7].
• Although CD23 and CD72 are well-known B-cell signalling molecules, the intracellular signal transduction pathways through which they operate remain poorly elucidated [8].
• In resting platelets, as in B lymphocytes, CD72 is associated with the protein tyrosine phosphatase SHP-1 [9].
• We also show that the surface expression of sema4D and CD72 increases during platelet activation, followed by the gradual shedding of the sema4D extracellular domain [9].

Biological context of CD72

• Here we demonstrate that, in the BCR-expressing myeloma line J558L mu 3, CD72 expression reduces the BCR ligation-induced phosphorylation of the BCR component Ig alpha/Ig beta and its cytoplasmic effectors Syk and SLP-65 [10].
• Mouse CD100 plays a crucial role in both humoral and cellular immunity through ligation of the lymphocyte receptor, CD72 [11].
• Besides suggesting the potential involvement of B-1a lymphocytes in B-B cell interactions during T-independent B cell responses, our results indicate that CD5 and CD72 counterstructures play a functional role in the B cell compartment [2].
• The effect of CD5 ligation on apoptosis was studied in 27 newly diagnosed patients with B-CLL, in relation to the expression of surface IgM (sIgM), CD79b, CD38, CD72 and CD19 [12].
• Identity of human Lyb-2 and CD72 and localization of the gene to chromosome 9 [13].

Anatomical context of CD72

• We have investigated the role of human CD72 in mature B cell differentiation [1].
• Taken together, these data demonstrate that CD72 is a key molecule in regulating mature B cell differentiation, particularly in preventing the differentiation of naive B cells into plasma cells, thus blocking the production of low-affinity antibodies [1].
• Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses [11].
• Since all T cells express CD5 constitutively, these data also suggest the existence of another ligand for CD72 [14].
• In tissue, immunohistochemical staining revealed positivity for all known B-cell compartments; however, pulpa macrophages of the spleen and von Kupffer cells exhibited distinct positivity for CD72 also [4].

Associations of CD72 with chemical compounds

• This CD72 signaling also induced tyrosine phosphorylation of various proteins such as Blk [1].
• CD72 is a 45-kDa glycoprotein that is predominantly expressed on cells of the B lineage, except for plasma cells [15].
• Mature B cells lacking CD72 show enhanced Ca(2+) mobilization and are hyperproliferative in response to BCR ligation [16].
• Inositol lipid hydrolysis was found to be unperturbed, although a shallow rise in the basal level of intracellular free Ca2+ was provoked on engaging CD72 [17].

Physical interactions of CD72

• Recently, we reported that the CD5 protein can bind to the B cell antigen CD72 [18].
• The B-cell transmembrane protein CD72 binds to and is an in vivo substrate of the protein tyrosine phosphatase SHP-1 [19].

Regulatory relationships of CD72

• CD72 expression itself was found to be weak on resting B lymphocytes and was modestly enhanced following culture with IL 4 [20].
• Substrate phosphorylation was restored by expression of dominant negative mutants of SHP-1, whereas the SHP-1 mutants failed to enhance phosphorylation of the cellular substrates in the absence of CD72 [10].
• CD72 cross-linking promoted an increase in B cell activation and proliferation [1].
• CD72-mediated suppression of human naive B cell differentiation by down-regulating X-box binding protein 1 [1].
• We now report that engagement of CD72 by the IgG monoclonal antibody BU40 potentiates the capacity of IL-4--when used at optimal concentrations--to promote CD23 production in human B cells [21].

Other interactions of CD72

• Upon BCR ligation, SHP-1 has been shown to associate with the BCR, the cytoplasmic protein-tyrosine kinases Lyn and Syk, and the inhibitory co-receptors CD22 and CD72 [10].
• Engagement of CD72 had no effect on the IL-4-promoted hyperexpression of surface IgM [21].
• The findings are discussed with reference to observations made on the triggering of murine B lymphocytes through Lyb-2 and within the context of previously defined human B cell activation pathways [20].
• Interestingly, expression of CD27, whose signal induces the differentiation of B cells into plasma cells, was down-modulated by CD72 stimulation [1].
• The CD5 protein was effective at concentrations as low as 0.15 microM and its effect could be abolished by preincubation with soluble recombinant CD72 but not by preincubation with control proteins, indicating the specificity of the binding [18].

Analytical, diagnostic and therapeutic context of CD72

• Flow cytometry analysis and proliferation assays were used to determine 1) the ability of B-1a and B-2 cells to coexpress functionally relevant counterligands other than CD5 and CD72, and 2) the signaling capacity of CD5 and CD72 in terms of B cell activation and proliferation [2].
• Using a pig radiation hybrid panel we found the porcine CD72 gene to be located on chromosome 1q21-28 in a region syntenic to human chromosome 9 [22].
• Sequence analysis of CD72 mRNA showed significantly increased nucleotide mutations, including both nucleotide substitutions and deletions [23].
• Although the specificity for CD72 was clear from immunoblotting, transfection and other experiments, staining with this reagent was inhibited when cells were pretreated with an Fc receptor-blocking antibody (CD16/CD32 specific) [24].

References