CD72 Down-Modulates BCR-Induced Signal Transduction and Diminishes Survival in Primary Mature B Lymphocytes

Li, Daniel H.; Tung, James W.; Tarner, Ingo H.; Snow, Andrew L.; Yukinari, Tsuyoshi; Ngernmaneepothong, Rachel; Martinez, Olivia M.; Parnes, Jane R.

doi:10.4049/jimmunol.176.9.5321

Cited by 34 publications

(30 citation statements)

References 36 publications

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“…In agreement with these results, SHP-1 has been found constitutively associated with the BCR complex and plays an inhibitory role in B cell signaling through ITIM-bearing inhibitory coreceptors [15,16]. For example, CD22, Fc␥RII2B1, and CD72 may negatively regulate BCR signaling through recruitment of SHP-1 in human [17,18] and in murine B cells [19,20], respectively.…”

Section: Introductionsupporting

confidence: 53%

Pivotal Advance: CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner

Lobo

Zhang

Shively

2009

Journal of Leukocyte Biology

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Upon antigen binding, the BCR transduces a signal culminating in proliferation or in AICD of the B cell. Coreceptor engagement and subsequent modification of the BCR signal pathway are mechanisms that guide the B cell to its appropriate fate. For example, in the absence of coreceptor engagement, anti-sIgM antibodies induce apoptosis in the human Daudi B cell lymphoma cell line. ITIM-bearing B cell coreceptors that potentially may act as negative coreceptors include FcRgammaIIb, CD22, CD72, and CEACAM1 (CD66a). Although the role of CEACAM1 as an inhibitory coreceptor in T cells has been established, its role in B cells is poorly defined. We show that anti-sIgM antibody and PI3K inhibitor LY294002-induced apoptosis are reduced significantly in CEACAM1 knock-down clones compared with WT Daudi cells and that anti-sIgM treatment induced CEACAM1 tyrosine phosphorylation and association with SHP-1 in WT cells. In contrast, treatment of WT Daudi cells with anti-CD19 antibodies does not induce apoptosis and has reduced tyrosine phosphorylation and SHP-1 recruitment to CEACAM1. Thus, similar to its function in T cells, CEACAM1 may act as an inhibitory B cell coreceptor, most likely through recruitment of SHP-1 and inhibition of a PI3K-promoted activation pathway. Activation of B cells by anti-sIgM or anti-CD19 antibodies also leads to cell aggregation that is promoted by CEACAM1, also in a PI3K-dependent manner.

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Section: Introductionsupporting

confidence: 53%

Pivotal Advance: CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner

Lobo

Zhang

Shively

2009

Journal of Leukocyte Biology

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“…4A, 4B). However, a previous study demonstrated that BCR ligationinduced calcium response is enhanced in Cd72 2/2 B cells (15,16). Thus, CD72-mediated regulation of BCR signaling depends on experimental conditions.…”

Section: Discussionmentioning

confidence: 97%

“…It is already well established that CD72 is a negative regulator of BCR signaling (12)(13)(14)(15)(16). Expression of CD72 a negatively regulates both calcium signaling and ERK phosphorylation induced by BCR ligation in BAL17 cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…CD72 contains a C-type lectin-like domain in the extracellular region and an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region (11)(12)(13). CD72 negatively regulates BCR signaling by recruiting SH2-containing tyrosine phosphatase-1 at the ITIM (12)(13)(14)(15)(16). In mice, four allelic forms of CD72 (i.e., CD72 , and CD72 d are highly homologous (18,19).…”

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confidence: 99%

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Cd72c Is a Modifier Gene that Regulates Faslpr-Induced Autoimmune Disease

Hou

Sato-Hayashizaki

et al. 2013

The Journal of Immunology

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Although modifier genes are extensively studied in various diseases, little is known about modifier genes that regulate autoimmune diseases. Autoimmune disease caused by the Faslpr mutation depends on the genetic background of mouse strains, suggesting a crucial role of modifier genes. MRL/MpJ-Faslpr (MRL/lpr) and AKR/lpr mice develop severe and mild lupus-like autoimmune disease, respectively, whereas this mutation does not cause disease on C57BL/6 (B6) or C3H background. Both MRL and AKR carry the same haplotype of the Cd72 gene encoding an inhibitory BCR coreceptor (CD72c), and CD72c contains several amino acid substitutions and a deletion in the extracellular region compared with CD72a and CD72b. To address the role of Cd72c locus in the regulation of Faslpr-induced autoimmune disease, we generated B6.CD72c/lpr and MRL.CD72b/lpr congenic mice. Introduction of the chromosomal interval containing Cd72c did not cause disease in B6 mice by itself, but caused development of lupus-like disease in the presence of Faslpr on B6 background, clearly demonstrating that this interval contains the modifier gene that regulates Faslpr-induced autoimmune disease. Conversely, MRL.CD72b/lpr congenic mice showed milder disease compared with MRL/lpr mice. We further demonstrated that Cd72c is a hypofunctional allele in BCR signal inhibition and that CD72 deficiency induces severe autoimmune disease in the presence of Faslpr. These results strongly suggest that the Cd72c is a crucial modifier gene that regulates Faslpr-induced autoimmune disease due to its reduced activity of B cell signal regulation.

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“…Signaling through the BCR on B-cells can be regulated by the inhibitory receptor FcγRIIb [9,10]. FcγRIIb belongs to the low affinity FcγRII (CD32) family, which comprises three isoforms with highly homologous structure but opposing functions.…”

Section: Introductionmentioning

confidence: 99%

FcγRIIb expression in early stage chronic lymphocytic leukemia

Bosch

Mora

Vicente

et al. 2017

Leukemia & Lymphoma

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In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d Moreover, patients with low FcγRIIb expression (69/155, 44.5%) required therapy earlier than those with high FcγRIIb expression (86/155, 55.5%) (median 151.4 months vs. not reached; p=0.071). These results encourage further investigation on the role of FcγRIIb in CLL biology and prognostic significance in larger series of patients.

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CD72 Down-Modulates BCR-Induced Signal Transduction and Diminishes Survival in Primary Mature B Lymphocytes

Cited by 34 publications

References 36 publications

Pivotal Advance: CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner

Pivotal Advance: CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner

Cd72c Is a Modifier Gene that Regulates Faslpr-Induced Autoimmune Disease

FcγRIIb expression in early stage chronic lymphocytic leukemia

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