Co‐cross‐linking of surface immunoglobulin Fcγ receptors on B lymphocytes uncouples the antigen receptors from their associated G protein

Rigley, Kevin P.; Harnett, Margaret M.; Klaus, G. G. B.

doi:10.1002/eji.1830190311

Cited by 46 publications

(24 citation statements)

References 22 publications

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“…Fc␥RII is a low affinity receptor for IgG that binds only IgG immune complexes and is expressed on a diverse range of cells such as monocytes, macrophages, neutrophils, eosinophils, platelets, and B cells (1)(2)(3). Fc␥RII is involved in a number of immune responses including antibody-dependent cell-mediated cytotoxicity, clearance of immune complexes, release of inflammatory mediators, and regulation of antibody production (1)(2)(3)(4)(5)(6).…”

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Multiple Regions of Human FcγRII (CD32) Contribute to the Binding of IgG

Hulett

Witort

Brinkworth

et al. 1995

Journal of Biological Chemistry

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The low affinity receptor for IgG, Fc␥RII (CD32), has a wide distribution on hematopoietic cells where it is responsible for a diverse range of cellular responses crucial for immune regulation and resistance to infection. Fc␥RII is a member of the immunoglobulin superfamily, containing an extracellular region of two Ig-like domains. Cell surface receptors for the Fc portion of IgG (Fc␥R) are expressed on most hematopoietic cells, and through the binding of IgG they play a key role in homeostasis of the immune system and host protection against infection. Three structurally related but functionally distinct classes of Fc␥R have been defined: Fc␥RI, Fc␥RII, and Fc␥RIII (1-3). Fc␥RII is a low affinity receptor for IgG that binds only IgG immune complexes and is expressed on a diverse range of cells such as monocytes, macrophages, neutrophils, eosinophils, platelets, and B cells (1-3). Fc␥RII is involved in a number of immune responses including antibody-dependent cell-mediated cytotoxicity, clearance of immune complexes, release of inflammatory mediators, and regulation of antibody production (1-6).The extracellular region of Fc␥RII comprises two Ig-like disulfide-bonded extracellular domains that are related to the Ig superfamily proteins and are most closely related to the C2 set of Ig domains (7-12). The two Ig-like domain extracellular region of Fc␥RII is structurally conserved in all of the Ig superfamily leukocyte FcRs (including Fc␥RI, Fc␥RIII, Fc⑀RI, and Fc␣RI) and presumably represents an Ig-interactive motif (13-17). The elucidation of the molecular basis of FcR-Ig interactions is fundamental for understanding the mechanisms by which these receptors mediate biological functions such as activation of inflammatory cells, induction of cytokine release, and destruction of pathogens. In previous studies we utilized chimeric Fc receptors to identify the IgG binding region of human Fc␥RII (18,19 (20). However, despite the direct demonstration of only a single region involved in the binding of IgG, there is compelling evidence to suggest that other regions of Fc␥RII contribute to binding. A genetic polymorphism of human Fc␥RIIa, the so called "responder/non-responder" system, results in an amino acid substitution in domain 2 at residue 131 (Arg 3 His), which has been shown to influence the binding of mouse . Similarly, in the mouse a genetic polymorphism of Fc␥RII, identified as differences at residues 116 and 161, defines the epitope of the anti-Ly17.2 mAb 1 that blocks the binding of IgG to this receptor (24, 25). Our previous molecular modeling studies of Fc␥RII domain 2 (wherein the Asn 154 -Ser 161 binding region was located to an exposed loop region; the F/G loop) suggest that these functionally important amino acid changes are situated in the B/C and CЈ/E loops (containing residues 116 and 131, respectively), which are juxtaposed to the F/G loop (contains residue 161) at or near the interface with domain 1 (20). Furthermore, the studies using chimeric Fc␥RII/Fc⑀RI receptors have identified three regions i...

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confidence: 99%

Multiple Regions of Human FcγRII (CD32) Contribute to the Binding of IgG

Hulett

Witort

Brinkworth

et al. 1995

Journal of Biological Chemistry

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“…This apparently uncouples the antigen receptors from GTP-dependent signal transduction (1)(2)(3). When human (4) or murine B cells (5) are activated by F(ab')2 fragments of anti-IgM or by phorbol ester, Ser phosphorylation of the Fc'yRII is induced.…”

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Protein-tyrosine kinase activity tightly associated with human type II Fc gamma receptors.

Sármay

Pecht

Gergely

1994

Proc. Natl. Acad. Sci. U.S.A.

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“…This inhibition is dependent on co-crosslinking sIg and FcRII and is manifested by uncoupling sIg from the G protein G,, thereby inhibiting the release of InsP3 [8]. It isinterestingthat, like anti-CD19,whole anti-Ig also permits exit of B cells from Go to the early GI phase of the cell cycle [lo].…”

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confidence: 99%

Inhibition of B cell proliferation with anti‐CD19 monoclonal antibodies: anti‐CD19 antibodies do not interfere with early signaling events triggered by anti‐IgM or interleukin 4

Rigley

Callard

1991

Eur J Immunol

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The 95-kDa antigen recognized by the anti-CD19 panel of monoclonal antibodies is found on the surface of most cells of the B cell lineage. Anti-CD19 antibodies inhibit B cell proliferation in response to anti-Ig plus interleukin 4 (IL4), but enhance the response to mitogenic concentrations of either phorbol 12-myristate 13-acetate (PMA) or Epstein-Barr virus. This dichotomy in the effect of anti-CD19 antibodies suggested that the inhibitory action may be directed at the transmembrane signaling pathways utilized by anti-IgM and IL4. To investigate this hypothesis, an attempt was made to determine the mechanism of signal transduction utilized by the CD19 antigen, and elucidate its effect on transmembrane signaling invoked by anti-immunoglobulin and IL4. Binding of anti-CD19 antibody to B cells did not promote activation of either the phosphoinositide or cAMP signaling pathways. In addition, anti-CD19 antibody did not inhibit phosphatidylinositol bisphosphate (PIP2) hydrolysis induced by anti-IgM or IL4, nor did it interfere with cAMP induction by IL4. We also found that anti-CD19 antibody inhibited PMA plus calcium ionophore-induced B cell proliferation. This evidence indicates that anti-CD19 mAb interrupts the signaling cascade at a point distal to receptor-mediated breakdown of PIP2 and/or activation of adenyl cyclase. This conclusion was fully consistent with experiments in which anti-CD19 antibody was shown to inhibit DNA but not RNA synthesis, and the observation that anti-CD19 antibody must be present between 6 h and 20 h after the initiation of the culture suggesting that anti-CD19 mAb exerts its inhibitory effect in late G0 or G1, after the initial signaling events.

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Co‐cross‐linking of surface immunoglobulin Fcγ receptors on B lymphocytes uncouples the antigen receptors from their associated G protein

Cited by 46 publications

References 22 publications

Multiple Regions of Human FcγRII (CD32) Contribute to the Binding of IgG

Multiple Regions of Human FcγRII (CD32) Contribute to the Binding of IgG

Protein-tyrosine kinase activity tightly associated with human type II Fc gamma receptors.

Inhibition of B cell proliferation with anti‐CD19 monoclonal antibodies: anti‐CD19 antibodies do not interfere with early signaling events triggered by anti‐IgM or interleukin 4

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