Augmented humoral and anaphylactic responses in FcγRII-deficient mice

Takai, Toshiyuki; Ono, M.; Hara, Masaki; Ohmori, Hitoshi; Ravetch, Jeffrey V.

doi:10.1038/379346a0

Cited by 777 publications

(599 citation statements)

References 16 publications

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“…32,33 Indeed, the balance between the stimulating and inhibiting signals has to be tightly regulated to maintain immune homeostasis, and autoimmune disorders have been observed in mice with targeted disruption of inhibitory Fc receptor in the appropriate genetic background. [34][35][36][37][38][39][40] Taken together, our data establish the physical relationship between the stimulatory receptors (Fc␥RIIA, Fc␥RIIIA, Fc␥RIIIB and Fc␥RIIC) and the inhibitory Fc␥RIIB. They establish a dense SNP map which will facilitate the discovery of genetic variations underlying susceptibility to autoimmune and other diseases.…”

Section: Discussionsupporting

confidence: 70%

Genomic organization of classical human low-affinity Fcγ receptor genes

Edberg

et al. 2002

Genes Immun

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Section: Discussionsupporting

confidence: 70%

Genomic organization of classical human low-affinity Fcγ receptor genes

Edberg

et al. 2002

Genes Immun

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“…In fact, crosslinking of BCR by antigen gives rise to a sequence of intracellular events that leads to the proliferation and\or differentiation of the cells followed by antibody production. In contrast, the ligation of BCR to FcγRIIB, a low-affinity receptor for IgG, leads to a dominant-negative signal that inhibits B-cell activation [2][3][4]. These findings support a model in which FcγRIIB provides a powerful mechanism for B-cells to discriminate between free antigen and antigen-antibody immune complex and can thus serve to prevent the production of excess immunoglobulin.…”

Section: Introductionsupporting

confidence: 53%

Distribution of the Src-homology-2-domain-containing inositol 5-phosphatase SHIP-2 in both non-haemopoietic and haemopoietic cells and possible involvement of SHIP-2 in negative signalling of B-cells

Muraille

Pesesse

Kuntz

et al. 1999

Biochemical Journal

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The termination of activation signals is a critical step in the control of the immune response; perturbation of inhibitory feedback pathways results in profound immune defects culminating in autoimmunity and overwhelming inflammation. FcγRIIB receptor is a well described inhibitory receptor. The ligation of B-cell receptor (BCR) and FcγRIIB leads to the inhibition of B-cell activation. Numerous studies have demonstrated that the SH2-domain-containing inositol 5-phosphatase SHIP (referred hereto as SHIP-1) is essential in this process. The cDNA encoding a second SH2-domain-containing inositol 5-phosphatase, SHIP-2, has been cloned [Pesesse, Deleu, De Smedt, Drayer and Erneux (1997) Biochem. Biophys. Res. Commun. 239, 697-700]. Here we report the distribution of SHIP-2 in mouse tissues: a Western blot analysis of mouse tissues reveals that SHIP-2 is expressed in both haemopoietic and non-haemopoietic cells. In addition to T-cell and B-cell lines, spleen, thymus and lung are shown to coexpress SHIP-1 and SHIP-2. Moreover, SHIP-2 is detected in fibroblasts, heart and different brain areas. SHIP-2 shows a maximal tyrosine phosphorylation and association to Shc after ligation of BCR to FcγRIIB but not after stimulation of BCR alone. Our results therefore suggest a possible role for SHIP-2 in the negative regulation of immunocompetent cells.

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“…Mice deficient in FCGR2B with no Fc␥RIIb expression have elevated serum Ig levels and enhanced anaphylactic responses (14). On a susceptible genetic background, mice deficient in FCGR2B develop antinuclear autoantibodies, glomerulonephritis, and other lupus-like symptoms (15).…”

Section: T He Only Inhibitory Igg Fcr In the Classical Fcr Family (1mentioning

confidence: 99%

Expression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus

Yang

et al. 2007

The Journal of Immunology

161

150

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FcγRIIb (CD32B, Online Mendelian Inheritance in Man 604590), an IgG FcR with a tyrosine-based inhibitory motif, plays a critical role in the balance of tolerance and autoimmunity in murine models. However, the high degree of homology between FcγRIIb and FcγRIIa in humans and the lack of specific Abs to differentiate them have hampered study of the normal expression profile of FcγRIIb and its potential dysregulation in autoimmune diseases such as systemic lupus erythematosus (SLE). Using our newly developed anti-FcγRIIb mAb 4F5 which does not react with FcγRIIa, we found that FcγRIIb is expressed on the cell surface of circulating B lymphocytes, monocytes, neutrophils, myeloid dendritic cells (DCs), and at very low levels on plasmacytoid DCs from some donors. Normal donors with the less frequent 2B.4 promoter haplotype have higher FcγRIIb expression on monocytes, neutrophils, and myeloid DCs similar to that reported for B lymphocytes, indicating that FcγRIIb expression on both myeloid and lymphoid cells is regulated by the naturally occurring regulatory single nucleotide polymorphisms in the FCGR2B promoter. FcγRIIb expression in normal controls is up-regulated on memory B lymphocytes compared with naive B lymphocytes. In contrast, in active SLE, FcγRIIb is significantly down-regulated on both memory and plasma B lymphocytes compared with naive and memory/plasma B lymphocytes from normals. Similar down-regulation of FcγRIIb on myeloid-lineage cells in SLE was not seen. Our studies demonstrate the constitutive regulation of FcγRIIb by natural gene polymorphisms and the acquired dysregulation in SLE autoimmunity, which may identify opportunities for using this receptor as a therapeutic target.

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Augmented humoral and anaphylactic responses in FcγRII-deficient mice

Cited by 777 publications

References 16 publications

Genomic organization of classical human low-affinity Fcγ receptor genes

Genomic organization of classical human low-affinity Fcγ receptor genes

Distribution of the Src-homology-2-domain-containing inositol 5-phosphatase SHIP-2 in both non-haemopoietic and haemopoietic cells and possible involvement of SHIP-2 in negative signalling of B-cells

Expression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus

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