Soluble CD16 in plasma cell dyscrasias.

Soluble forms of Fc gammaR type III (sFc gammaRIII or sCD16) are present in many biological fluids. Their main ligand is IgG in the form of complexes. In plasma, sCD16 essentially derive from cleavage of membrane CD16 (or Fc gammaRIII) present on neutrophils and, to a lesser extent, on NK cells. Determination of sCD16 serum level during monoclonal gammopathies has demonstrated markedly reduced levels in multiple myeloma and in monoclonal gammopathy of undetermined significance (MGUS) rapidly evolving to multiple myeloma, compared to stable MGUS or controls, indicating a prognostic value for this biological parameter. The biology and functions of sCD16 are described, together with the biological significance of modifications of the sCD16 serum level in monoclonal gammopathies.

Purification of human dihydro-orotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomide.

Leflunomide is currently in phase-III clinical trials for the treatment of rheumatoid arthritis. In this study, we have focused our efforts on the study of the mechanism of action of the active metabolite of leflunomide, A77 1726, in cells and tissue of human origin. The human high-affinity binding protein for radiolabelled A77 1726 was purified from solubilized U937 membranes by following the binding activity through the purification process and was characterized as the mitochondrial enzyme dihydro-orotate dehydrogenase (DHO-DH). The human and murine enzyme displayed identical pI and molecular mass values on SDS/PAGE (43 kDa), which contrasts notably with previous reports suggesting a molecular mass of 50 kDa for the human enzyme. DHO-DH activity was inhibited by A77 1726 and its analogue HR325 with similar potency in U937 and human spleen membrane preparations. HR325 was found to be anti-proliferative for phytohaemagglutinin-stimulated human peripheral blood mononuclear cells, at the same concentrations that caused accumulation of DHO and depletion of uridine. Supplementation of the cultures with exogenous uridine led to partial abrogation of the anti-proliferative effect. This is in line with our recent demonstration that the anti-proliferative effect in vitro of A77 1726 on lipopolysaccharide-stimulated mouse spleen cells was mediated by DHO-DH inhibition [Williamson, Yea, Robson, Curnock, Gadher, Hambleton, Woodward, Bruneau, Hambleton, Moss et al., (1995) J. Biol. Chem. 270, 22467-22472]. Thus, DHO-DH inhibition by A77 1726 and its analogues is responsible for the anti-proliferative effects in vitro of the compounds on human cells and is likely to be responsible for some of its effects in vivo.

Characterization of anti-mouse Fc gamma RII single-chain Fv fragments derived from human phage display libraries.

BACKGROUND: Few antibodies are available to study the function of the Fc gamma RII murine immunoglobulin receptor. Human phage display libraries represent a potential source of single-chain Fv (sFv) to facilitate the study of the Fc gamma RII murine immunoglobulin receptor. OBJECTIVES: To isolate human sFv specific for mouse Fc gamma RII. STUDY DESIGN: Two human phage display libraries were selected for reactivity to mouse Fc gamma RII. Those human anti-mouse Fc gamma RII sFv that were derived from the libraries were characterized with respect to kinetics, cellular binding, epitope specificity and amino acid sequence. RESULTS: Nine anti-mouse Fc gamma RII sFv molecules were isolated from two human phage display libraries (Marks et al., J Mol Biol 1991;222:581-597; Sheets et al., Proc Natl Acad Sci USA, in press). Surface plasmon resonance (SPR) analysis revealed that the human anti-mouse Fc gamma RII sFv had off-rates ranging from 10(-2) to 10(-3) s-1, with KD values calculated to range between 10(-7) and 10(-9) M. The binding of the FITC-labeled human anti-mouse Fc gamma RII sFv to mouse peritoneal neutrophils was not detected by flow cytometry, due to the rapid off-rates of these monomeric proteins. However, when the human anti-mouse Fc gamma RII sFv were coated on yellow-green latex particles, all of the human sFv were found to specifically bind to mouse peritoneal neutrophils. Deglycosylation of mouse Fc gamma RII did not diminish the binding of these sFv, suggesting that the sFv molecules recognize a polypeptide epitope on murine Fc gamma RII. In contrast, denaturation of mouse Fc gamma RII dramatically reduced the binding of the human sFv, suggesting that the epitopes are conformational. Sequence analysis of the human anti-mouse Fc gamma RII sFv revealed a high degree of structural similarity among the nine sFv. The DP73 VH gene segment was utilized by four of the nine sFv, while seven of the nine sFv contained the DPL16 V lambda gene segment. The sequence similarities between these sFv suggested that several of the human sFv may recognize a common epitope on mouse Fc gamma RII. Epitope mapping studies demonstrated that eight of the nine human anti-mouse Fc gamma RII sFv recognized overlapping epitopes. All of these human anti-mouse Fc gamma RII sFv competed with the 2.4G2 rat monoclonal anti-mouse Fc gamma RII/III antibody for binding with mouse Fc gamma RII, suggesting that the targeted epitopes reside in or near the Fc binding pocket of mouse Fc gamma RII. CONCLUSIONS: The availability of novel sFv recognizing mouse Fc gamma RII will facilitate the study of receptor triggering events. Such sFv may prove useful to engage murine Fc gamma RII for targeted cytotoxicity or immunization strategies.

Effect of TGF-beta1 on cell cycle regulatory proteins in LPS-stimulated normal mouse B lymphocytes.

The cell cycle events accompanying TGF-beta1-induced growth arrest of normal mouse resting B lymphocytes stimulated by LPS were investigated. We showed that TGF-beta1 prevents the retinoblastoma protein (pRb) phosphorylation and induces growth arrest in mid- to late G1. To explore the molecular basis of the effect of TGF-beta1, we analyzed the in vitro kinase activities of cyclin/cyclin-dependent kinase (cdk) complexes involved in the progression through G1 phase and in the G1/S transition, by using the glutathione S-transferase-pRb fusion protein as a substrate. Cdk2-associated kinase activity was strongly induced in mitogen-treated B cells. It was dramatically inhibited by TGF-beta1 as were the cyclin E- and cyclin A-dependent kinase activities. TGF-beta1 treatment had no significant effect on the expression of two G1/S phase proteins, cyclin E and cdk2. In contrast, the appearance of cyclin A, occuring in late G1 phase, was almost totally inhibited by TGF-beta1. We also showed that expression of the cdk inhibitor protein p27Kip1 decreased as cells progressed through the G1 phase. An accumulation of p27 was found in TGF-beta1-treated cells, showing that TGF-beta1 prevented LPS-induced decline of p27. Finally we found that the lack of kinase activity associated with cyclin E/cdk2 complexes was correlated with increased amounts of cdk2- and cyclin E-bound p27. Overall, these results suggest that both cyclin A and cdk2 may be active participants in the TGF-beta1-induced cell cycle arrest in normal mouse B cells and indicate the involvement of p27 in this mechanism.

Affinity of the interaction between Fc gamma receptor type III (Fc gammaRIII) and monomeric human IgG subclasses. Role of Fc gammaRIII glycosylation.

Binding of the Fc region of IgG antibodies to low affinity Fc gamma receptors (Fc gammaR) triggers important effector functions in the immune system. The type IIIb Fc gammaR (Fc gammaRIIIb or CD16) is a heavily glycosylated protein anchored to the membrane of neutrophils by a glycosylphosphatidylinositol link. This receptor contributes to cell activation by IgG immune complexes. To better understand the nature of the ligand-receptor association, we have studied the affinity and kinetics of the interaction between human IgG subclasses and two soluble forms of Fc gammaRIIIb (sFc gammaRIIIb or sCD16) corresponding to the 188 N-terminal amino acids of the extracellular region of the receptor, a glycosylated one made in eucaryotic cells (euc.sCD16) and a non-glycosylated one (proc.sCD16) made in Escherichia coli. Experiments using a BIAcore instrument, to measure protein binding in real time, showed that monomeric human IgG1 and IgG3, but not IgG2, IgG4, IgA and divalent antigen-binding fragments (F(ab')2) of IgG1, bound to immobilized euc.sCD16 with an affinity constant (K(A)) of 1.3 +/- 0.6 x 10(6) M(-1) and 2.6 +/- 0.4 x 10(5) M(-1), respectively. The affinity constant of proc.sCD16 for human IgG1 was in the same range (1.1 +/- 0.2 x 10(6) M(-1)), whereas that for human IgG3 was twofold higher (4.2 +/- 0.4 x 10(5) M(-1)). The specificity of the non-glycosylated receptor for human IgG subclasses bound to Sepharose was IgG1 > IgG3 >> IgG4 >>> IgG2. Thus, the extracellular polypeptide of Fc gammaRIIIb dictates the interaction of the receptor with IgG subclasses although glycosylation plays an inhibitory role in the interaction with human IgG3.

Characterization of soluble gp130 released by melanoma cell lines: A polyvalent antagonist of cytokines from the interleukin 6 family.

gp130 acts as a common transducing signal chain for all receptors belonging to the interleukin (IL)-6 receptor family. The IL-6-related cytokines [IL-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor, ciliary neurotrophic factor, and cardiotrophin] often modulate tumor phenotype and control the proliferation of many tumor cell lines. We demonstrate that melanoma cell lines release, in vitro and in vivo (when transplanted in nude mice), soluble gp130 (sgp130), a potential antagonist of cytokines from the IL-6 family. Biochemical analysis revealed that sgp130 derived from melanoma patients' sera or from culture supernatants of melanoma cell lines is a Mr 104,000 protein that resolved after deglycosylation as a Mr 58,000 protein. PCR and Northern blot analysis only identified one gp130 membrane mRNA, suggesting that the soluble form of gp130 is generated by proteolytic cleavage. OSM reproducibly increases sgp130 released by melanoma cell lines, whereas leukemia inhibitory factor stimulates the production of sgp130 in only one of three cell lines tested. This tumor-derived sgp130 is functional because it binds in solution to the IL-6-soluble IL-6 receptor (gp80) complex. Recombinant sgp130 inhibits the growth inhibitory activity of the IL-6-soluble IL-6 receptor complex and OSM on some melanoma cell lines. Therefore, this soluble gp130 represents a natural antagonist of cytokines from the IL-6 family.

Soluble CD16 (sCD16), a marker of malignancy in individuals with monoclonal gammopathy of undetermined significance (MGUS).

There are no well-defined host markers to determine which patients with a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) will progress to multiple myeloma (MM). In this preliminary study we measured plasmatic soluble Fe gamma receptor type III (sFe gamma RIII or sCD16) in 54 individuals with MGUS. 35 patients with multiple myeloma (MM) and 29 healthy controls. We confirmed, through receiver operating characteristic (ROC) curve analysis, that a low level of sCD16 discriminates MM patients from controls. Indeed, for a sCD16 value of 1.3 micrograms/ml, the sensitivity, as well as the specificity, of this discrimination were both equal to 83%, i.e. 83% of MM patients had a plasmatic sCD16 value < 1.3 micrograms/ml compared with only 17% of controls. Moreover, ROC curve analysis showed that a low sCD16 level also identifies among MGUS patients a subgroup of patients who rapidly progress towards multiple myeloma: in this comparison, for a sCD16 level of 1.3 micrograms/ml. sensitivity and specificity were 70% and 79% respectively. Therefore a low sCD16 level in MGUS indicated a high likelihood of rapid evolution of MM. In contrast to sCD16, soluble IL-6R did not appear to be discriminant in this study.

Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum.

A quantitative trait locus for increased IgG serum levels in the NOD mouse strain was mapped to distal chromosome 1, close to the fcgr2 locus encoding the low-affinity type II receptor for the Fc portion of IgG (Fc gamma RII). Expression of membrane-inserted (b2) and soluble (b3) isoforms of Fc gamma RII was strongly decreased in macrophages of NOD compared with C57BL/6 (B6) mice. In contrast, B cell-specific (Fc gamma RIIb1) isoform was only slightly decreased and Fc gamma RIII was not altered. This Fc gamma RII regulatory defect was cis-encoded by fcgr2 or by a closely linked locus, occurred at the mRNA level, and was associated with multiple mutations in the fcgr2 gene promoter. In relation with this defect, binding of IgG1- and IgG2b- but not IgG2a-opsonized RBC by macrophages of NOD and congenic B6.NOD-fcgr2 mice was severely impaired, but was normal in macrophages of NOD.B6-fcgr2 congenic mice, indicating that Fc gamma RII plays a nondispensable role in binding of IgG1 and IgG2b isotypes. Likewise, serum levels of IgG1 and IgG2b but not IgG2a were up-regulated in NOD compared with NOD.B6-fcgr2 congenic mice. These findings indicate that macrophage Fc gamma RII may regulate serum IgG1 and IgG2b through their catabolism, and validate the NOD strain as a model to investigate the functions of Fc gamma RII isoforms.

Contribution of the intracellular domain of murine Fc-gamma receptor type IIB1 to its tumor-enhancing potential.

We have previously shown that Fc gamma receptor type II B1 (Fc(gamma)RIIB1), when expressed on non-lymphoid tumor cells, significantly enhanced their tumorigenic phenotype. This study elucidates the role of the intracellular domain of Fc(gamma)RIIB1 in the enhancement of the malignant phenotype of polyoma-transformed 3T3 cells. We investigated the tumorigenic potential conferred by different variants of the receptor: Fc(gamma)RIIB1, a full-length receptor (B1) whose intracellular region is encoded by exons 8, 9 and 10; Fc(gamma)RIIB2, a spliced variant (B2) whose cytoplasmic domain comprises exons 9 and 10 and lacks exon 8; and Fc(gamma)RIIB1-CT53, a deleted mutant whose cytoplasmic domain contains the fragment encoded by exon 8 alone. We have investigated various properties of cells transfected with each of the above variants: tumorigenicity in syngeneic mice, formation of colonies in soft agar, growth rate, production of soluble receptor and capping of the ligand-bound receptor. Results show that while the presence of exon 8 did not enhance growth rate in vitro or production of soluble Fc(gamma)R, it did enhance the tumorigenic phenotype of transfected cells (both in vivo and in vitro growth in soft agar). B1-expressing cells exhibited a significantly higher tumorigenic phenotype than B2 cells. The presence of exon 8 alone (CT53 mutant) conferred the transfected cells a higher tumorigenic phenotype than Fc(gamma)R-negative control cells but lower than intact B1 or B2 cells, indicating that the presence of B1-specific exon 8 is not sufficient but that the presence of an intact B1 intracellular domain is essential, for conferring the high tumorigenicity phenotype upon cells. We conclude that the capping, following ligand binding contributed by exon 8, and the function contributed by the specific localization of exons 9 and 10 in B1 cells may determine their malignant phenotype.

Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation through interaction with complement receptors.

The type III-B Fcgamma receptor (FcgammaRIII-B) is a glycosyl-phosphatidylinositol-linked receptor found on human neutrophils. A soluble form of FcgammaRIII-B (sCD16) corresponding to the extracellular region of the receptor circulates in plasma. In the present work, we have identified membrane receptors for sCD16. Soluble CD16 bound to CR3 (CDllb/CD18)- and CR4 (CDllc/CD18)- positive leukocytes and cell lines, the labeling was inhibited by anti-CD11b, CD11c or CD18 mAbs, and the up-regulation of CR3 and CR4 led to an increased fixation of sCD16. Transfected eukaryotic cells expressing recombinant CD11b/CD18 or CD11c/CD18 heterodimers but not those expressing CD11a/CD18 bound sCD16. Moreover, the lectin-like binding site of CR3 is probably involved in the interaction with sCD16, as suggested by inhibition studies using mAbs against CR3 or sugars such as N-acetyl D-glucosamine, alpha- or beta-methyl D-glucoside, alpha- or beta-methyl D-mannoside, or zymosan. Thus, the complement receptors CR3 and CR4 are membrane receptors for sCD16. Through this interaction, sCD16 induces a CR3-dependent production of IL-6 and IL-8 by monocytes. These results suggest that sCD16 plays a regulatory role in inflammatory processes and provide a molecular basis for the interaction between FcgammaRIII-B and CR3 described on the cell membrane.

The murine Fc-gamma (Fc gamma) receptor type II B1 is a tumorigenicity-enhancing factor in polyoma-virus-transformed 3T3 cells.

The murine receptor for the Fc portion of IgG is a molecule expressed by cells of the immune system. This study suggests the hypothesis that Fc gamma receptor type II B I (Fc gamma RIIB I) functions as a progression-enhancing factor when expressed ectopically on non-lymphoid tumor cells. It has been shown previously that BALB/c 3T3 cells transformed in vitro with polyoma virus (PyV) do not express Fc gamma RII but acquire the expression of this receptor following an in vivo passage in syngeneic mice. The specific Fc gamma RII transcript present in tumor cells was identified in this report as Fc gamma RIIB I (BI). In order to determine whether or not the ectopically expressed Fc gamma RII plays a role in the progression of these transformed cells, PyV-transformed 3T3 cells were transfected with BI-cDNA. The BI transfected cells were tested for their ability to form local tumors in syngeneic mice, as compared to transfected cells which express the co-transfecting neomycine resistance (neores) DNA alone or together with the lacZ gene. Fc gamma RIIB I expressors exhibited a significantly higher tumorigenic phenotype than FcR-negative controls, though both types of cells exhibited the same growth curve in vitro. The ability of Fc gamma RIIB I to act as a potentially tumorgenicity-enhancing factor was also demonstrated as Fc gamma RII was expressed by tumor cells, originating from inoculated Fc gamma RIIB I-transfected cells, or from inoculation of a mixture of receptor-positive and -negative cells. B I-expressing cells dominated the tumor-cell population over non-expressors. This dominance strengthened the hypothesis that FcR plays a role in tumor progression in vivo.

Prognostic value of cytokine and soluble Fc gamma receptor assays in oncology.

The clinical course of a cancer is influenced by the interaction of tumour cells with the patient's immune system. It is thus conceivable that immunological parameters may be used as markers of prognostic or predictive value. We report here that increased serum levels of IL-6 is a signal of poor prognosis and predicts unresponsiveness to immunotherapy in patients with metastatic melanoma. In cervical cancer, IL-6 produced by infiltrating macrophages is a marker of invasive cancer. In patients with multiple myeloma, the plasmatic levels of soluble Fc gamma receptors are markers of the disease, sCD16 being drastically decreased and sCD32 being slightly increased.

An alternative Fc gamma-receptor ligand: potential role in T-cell development.

Fetal pre-T cells express low-affinity receptors for IgG (Fc gamma R) at a developmental stage prior to the rearrangement and expression of immunoglobulin genes. The present studies investigated the possible functional significance of Fc gamma R on fetal pre-T cells. Between 13 and 17 days of fetal development a subpopulation of T-cell receptor-, Thy-1+ thymocytes express for gamma R. The same cells contain mRNA for several forms of Fc gamma R (Fc gamma RII beta 1, beta 2, and Fc gamma RIII). Concurrently, a Pgp-1-, Thy-1-, surface-immunoglobulin- fetal thymic cell binds recombinant soluble Fc gamma R. In principle this cell can interact with the pre-T cells through this counter-receptor. To test this possibility anti-Fc gamma RII/III antibody (2.4G2) was injected into pregnant mice and then into their offspring for 6 wk postpartum. The injected antibody induced a slight increase in the proportion of CD4 or CD8 single-positive, alpha/beta T cells in the thymus. However, in fetal thymic cultures in the presence of 2.4G2 or the recombinant soluble Fc gamma R there was an accelerated differentiation of thymocytes to single-positive, CD3-bright, heat-stable antigen-dull, alpha/beta T cells. These experiments show that Fc gamma Rs are present on pre-T cells during early fetal thymic development, and that a non-IgG ligand of the Fc gamma R is expressed concurrently on Thy- fetal thymocytes. Furthermore, the presumed interaction of Fc gamma R and the alternative ligand(s) influences T-cell development. IgG binding could be an adapted function of Fc gamma Rs, and, as shown for many members of the Ig super family, these receptors may have originally served as cell-cell recognition/interaction molecules required for hematopoietic development.

[Receptors for the Fc fragment of IgG (RFc gamma): membrane forms and soluble forms]. / Les récepteurs pour le fragment Fc des IgG (RFc gamma): formes membranaires et formes solubles.

Membrane and soluble forms of Fc gamma receptors play important role in immune reactions. Upon interaction with immune complexes, Fc gamma R transduce activation or inhibition signals via their intracytoplasmic portions. Soluble Fc gamma R contain the Fc gamma R ectodomain. They bind to the Fc portion of IgG and inhibit Fc dependent immune reactions. In addition, they bind directly to various cell types and regulate immune reactions.

Soluble Fc gamma receptors.

Soluble Fc gamma receptors have been identified in biological fluids of mice and humans. They are produced either by alternative splicing of the exon encoding the transmembrane region of the receptor (Fc gamma RII) or by proteolytic cleavage at the cell membrane (Fc gamma RII and Fc gamma RIII). They inhibit B cell proliferation and immunoglobulin production. Their concentrations in plasma seem to be modified during the development of certain diseases, as for instance in multiple myeloma, where plasma concentrations of soluble Fc gamma RIII are correlated with the stage of the disease.

Identification, in mouse macrophages and in serum, of a soluble receptor for the Fc portion of IgG (Fc gamma R) encoded by an alternatively spliced transcript of the Fc gamma RII gene.

Low affinity Fc gamma R are a heterogeneous group of glycoproteins which exist in transmembrane (TM) as well as in soluble forms. Two membrane isoforms of the murine type II Fc gamma R, Fc gamma RIIb1 and Fc gamma RIIb2, have been described. They result from the translation of alternatively spliced pre-mRNA, Fc gamma RIIb2 lacking sequences of the first intracytoplasmic domain (IC1). Soluble forms of Fc gamma R (sFc gamma R) have previously been shown to result from proteolysis of membrane receptors. We report here the identification, in macrophages, of a mRNA derived from the Fc gamma RII gene by splicing exons encoding the TM and IC1 domains, i.e. corresponding to a TM-deleted Fc gamma RIIb2 mRNA. A soluble protein possibly encoded by this mRNA was identified in macrophage supernatants. In accordance with Fc gamma R nomenclature, we propose to name this new Fc gamma RII isoform Fc gamma RIIb3. It is the most abundant sFc gamma R present in serum, as compared with sFc gamma R resulting from cleavage of membrane Fc gamma R.

Soluble Fc gamma R (sFc gamma R): detection in biological fluids and production of a murine recombinant sFc gamma R biologically active in vitro and in vivo.

Soluble forms of receptors for the Fc portion of IgG (sFc gamma R) were detected in biological fluids from mice and humans. In mouse bearing tumors, circulating amounts of sFc gamma R increased concurrently with tumor growth. Tumors secreting IgG2a, IgG2b or IgG3 led to a 5- to 10-fold increase in serum sFc gamma R levels whereas tumors secreting IgG1, IgGA or other types of tumors (non Ig B cell tumors, T cell lymphoma and a melanoma) increased 2- to 3-fold the levels of circulating sFc gamma R. In the human, sFc gamma R were also detected in whole unstimulated saliva. Levels of sFc gamma RII and of sFc gamma RIII were variable and did not seem to depend on the dental status of the individuals. Finally, a murine recombinant sFc gamma R (rsFc gamma R) composed of the two extracellular domains of Fc gamma RII was produced by culture of transfected L cells in bioreactors. The purified rsFc gamma R was found to inhibit antibody production in vitro in anti-SRBC responses and by cultures of small B cells stimulated by anti-IgM antibodies in the presence of IL-4 and IL-5. Moreover, the i.p. injection of this material into adult mice immunized with SRBC led to a decrease of IgG antibody production by splenocytes, as measured by a hemolytic plaque assay, and in serum, as measured by antigen-specific ELISA.

Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes.

B lymphocytes and macrophages express closely related immunoglobulin G (IgG) Fc receptors (Fc gamma RII) that differ only in the structures of their cytoplasmic domains. Because of cell type-specific alternative messenger RNA splicing, B-cell Fc gamma RII contains an insertion of 47 amino acids that participates in determining receptor function in these cells. Transfection of an Fc gamma RII-negative B-cell line with complementary DNA's encoding the two splice products and various receptor mutants indicated that the insertion was responsible for preventing both Fc gamma RII-mediated endocytosis and Fc gamma RII-mediated antigen presentation. The insertion was not required for Fc gamma RII to modulate surface immunoglobulin-triggered B-cell activation. Instead, regulation of activation involved a region of the cytoplasmic domain common to both the lymphocyte and macrophage receptor isoforms. In contrast, the insertion did contribute to the formation of caps in response to receptor cross-linking, consistent with suggestions that the lymphocyte but not macrophage form of the receptor can associate with the detergent-insoluble cytoskeleton.

[Demonstration of soluble IgG-Fc type II receptors (or s-Fc-gamma-II-R) in human whole saliva]. / Mise en évidence de récepteurs solubles de type II pour la partie Fc des IgG (ou RFc gamma IIs) dans la salive totale humaine.

Twenty human salivary samples from two groups of patients (with or without dental caries) were tested for the presence of soluble forms of Fc gamma receptors type II (sFc gamma RII): sFc gamma RII were detected by immunoblotting using a radiolabelled monoclonal antibody directed against human Fc gamma RII. These soluble forms specifically interact with the Fc portion of IgG and are produced by cells of the immune system (macrophages, neutrophils, Langerhans cells). This study showed that sFc gamma RII are present in human unstimulated saliva. The statistical analysis indicated that the relative amounts of sFc gamma RII in human unstimulated saliva are variable depending on the patient. No apparent association was found between the sFc gamma RII and the oral status of the patients.