Structural Bases of Fcγ Receptor Functions

Fridman, Wolf‐Herman; Bonnerot, Christian; Daëron, Marc; Amigorena, Sebastián; Teillaud, Jean‐Luc; Sautès, Catherine

doi:10.1111/j.1600-065x.1992.tb00625.x

Cited by 132 publications

(79 citation statements)

References 73 publications

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“…1 B), whereas in control B cells, the proliferative responses were significantly reduced when stimulated with whole anti-IgM Abs which have been shown to cross-link BCR with FcyP, IIB, a predominant form of Fcy receptors expressed on B cells (45)(46)(47). The results demonstrate that FcyRIIBmediated downregulation of BCP, signaling is not properly functional in the absence of Lyn, although it has not yet been studied whether Lyn is activated by cross-linking FcyRIIB.…”

Section: Prol!femtive Responses To Various Stimuli In Lyn -/-B Cellsmentioning

confidence: 99%

Altered antigen receptor signaling and impaired Fas-mediated apoptosis of B cells in Lyn-deficient mice.

Wang

Koizumi

Watanabe

1996

The Journal of Experimental Medicine

145

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SUlTIITIaryMice deficient in the src-related protein tyrosine kinase, Lyn, exhibit splenomegaly and accumulate lymphoblast-like and plasma cells in spleen as they age, resulting in elevated levels of serum IgM (10-20-fold of control) and glomerulonephritis due to the presence of immune complexes containing auto-reactive antibodies. It remains unclear, however, how antibodyproducing cells are accumulated in the lymphoid tissues of Lyn -/-mice.To elucidate the role of Lyn in B cell function, we have studied the proliferative responses to various stimuli and Fasmediated apoptosis in B cells from young Lyn -/-mice which do not yet show apparent abnormality such as splenomegaly. Compared with control B cells, Lyn -/-B cells were hyper responsive to anti-lgM-induced proliferation and defective in FcyRIIB-mediated suppression orB cell antigen receptor (BCR) signaling, indicating that Lyn is involved in the negative regulation of BCR signaling. In addition, the BCR-mediated signal in Lyn -/-B ceils, unlike that in control B cells, failed to act in synergy with either CD40-or IL-4 receptor-triggered signal in inducing a strong proliferative response, suggesting that the BCR signaling pathway in Lyn -/-B cells is altered from that in control B cells. Furthermore, Lyn -/-B cells were found to be impaired in the induction of Fas expression after CD40 ligation and exhibited a reduced susceptibility to Fas-mediated apoptosis. Moreover, BCR cross-linking in Lyn -/-B ceils suppressed Fas expression induced by costimulation with CD40 ligand and IL-4. Collectively, these results suggest that the accumulation of lymphoblast-like and plasma cells in Lyn -/-mice may be caused, in part, by the accelerated activation of B cells in the absence of Lyn, as well as the impaired Fasmediated apoptosis after the activation.T he B cell antigen receptor (BCR) 1 consists of membrane immunoglobulin M (IgM) non-covalently associated with disulfideqinked heterodimers of Igor and Ig[~ subunits which couple mlg to several protein tyrosine kinases (PTKs) (1). Cross-linking of the BCR rapidly activates two classes of PTKs: the src family kinases (Lyn, Fyn, Blk, Hck, and Lck) (2-5) and the Syk kinase (6, 7), resulting in the phosphorylation of several proteins (8, 9), including PTKs themselves, Igor and Ig[3 (10), phospholipase C-y (11), phosphatidylinositol (PI)-3 kinase (12, 13), the protooncogene product Vav (14-16), Ras GTPase-activating protein (17), Shc (18), and HS1 (19).The src-related kinase, Lyn, is expressed preferentially in hematopoietic cells and in cells of neural tissues (20,21). Lyn is physically associated with the BCR in B cells and is rapidly phosphorylated upon receptor cross-linking (2-5).1Abbreviations used in this paper: BCR, B cell antigen receptor; CD40L, CD40 ligand; Fc"/IIRB, B cell receptor for IgG Fc region; lgM, membrane immunoglobulin M; NMS, normal mouse serum; Pl, propidium iodide; PTK, protein tyrosine kinase; SHP-1, hematopoitic cell phosphatase; smlg, cell surface IgM.Lyn interacts with and phosphorylates the Syk ki...

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Section: Prol!femtive Responses To Various Stimuli In Lyn -/-B Cellsmentioning

confidence: 99%

Altered antigen receptor signaling and impaired Fas-mediated apoptosis of B cells in Lyn-deficient mice.

Wang

Koizumi

Watanabe

1996

The Journal of Experimental Medicine

145

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“…The α subunits of many of the Ig superfamily FcRs are found in multiple forms (Ravetch et al 1986, Stuart et al 1989, Qiu et al 1990, Ernst et al 1992reviewed in Ravetch & Kinet 1991, Fridman et al 1992, Hulett & Hogarth 1994. In the mouse, single genes encode each of the three classes of Fcγ R, whereas in humans, three Fcγ RI, three Fcγ RII, and two Fcγ RIII genes have been identified (reviewed in Ravetch 1994, Hulett & Hogarth 1994.…”

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confidence: 99%

Fc RECEPTORS AND THEIR INTERACTIONS WITH IMMUNOGLOBULINS

Raghavan

Björkman

1996

Annu. Rev. Cell Dev. Biol.

279

186

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Receptors for the Fc domain of immunoglobulins play an important role in immune defense. There are two well-defined functional classes of mammalian receptors. One class of receptors transports immunoglobulins across epithelial tissues to their main sites of action. This class includes the neonatal Fc receptor (FcRn), which transports immunoglobulin G (IgG), and the polymeric immunoglobulin receptor (pIgR), which transports immunoglobulin A (IgA) and immunoglobulin M (IgM). Another class of receptors present on the surfaces of effector cells triggers various biological responses upon binding antibody-antigen complexes. Of these, the IgG receptors (Fcγ R) and immunoglobulin E (IgE) receptors (Fc R) are the best characterized. The biological responses elicited include antibody-dependent, cell-mediated cytotoxicity, phagocytosis, release of inflammatory mediators, and regulation of lymphocyte proliferation and differentiation. We summarize the current knowledge of the structures and functions of FcRn, pIgR, and the Fcγ R and Fc RI proteins, concentrating on the interactions of the extracellular portions of these receptors with immunoglobulins.

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“…Receptors for the Fc portion of IgG (FcγRs) are a heterogeneous family of membrane-associated glycoproteins, which mediate various effector and regulatory functions such as the release of inflammatory regulator, endocytosis of the immune complex, and antibody-dependent cell-mediated cytotoxicity (ADCC) [1][2][3]. Human FcγRs are divided into three classes: FcγRI, FcγRII, and FcγRIII.…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Classification of N -Linked Oligosaccharides of the Extracellular Regions of Fcγ Receptor IIIb Expressed in Baby Hamster Kidney Cells

Kato¹

2014

J Glycomics Lipidomics

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Structural Bases of Fcγ Receptor Functions

Cited by 132 publications

References 73 publications

Altered antigen receptor signaling and impaired Fas-mediated apoptosis of B cells in Lyn-deficient mice.

Altered antigen receptor signaling and impaired Fas-mediated apoptosis of B cells in Lyn-deficient mice.

Fc RECEPTORS AND THEIR INTERACTIONS WITH IMMUNOGLOBULINS

Site-Specific Classification of N -Linked Oligosaccharides of the Extracellular Regions of Fcγ Receptor IIIb Expressed in Baby Hamster Kidney Cells

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