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At least 19 recordsLinked to original sources
PubMed1997

Expression of an Epstein-Barr-virus receptor and Epstein-Barr-virus-dependent transformation of human nasopharyngeal epithelial cells.

The human herpes virus Epstein-Barr (EBV) is clearly associated with African Burkitt's lymphoma and the undifferentiated form of nasopharyngeal carcinoma (NPC). EBV has been implicated in other types of lymphoma, as well as in some human breast cancers. However, its route of entry into epithelial cells is incompletely understood. We report here evidence that there is no gene alteration in the SCR 1 and 2 exons of EBVR/CR2 in human embryonic nasopharyngeal epithelial (HENE) cells and NPC cells and that SCR 1 and 2 mRNA could be detected in HENE cells, different differentiated NPC cell lines and well-differentiated NPC biopsies. None of 15 cases of poorly differentiated NPC cryosections has SCR 1 and 2 mRNA. We also provide evidence that transformation of HENE cells results from exposure to infectious EBV and that transformation is dependent on the presence of phorbol ester. These data suggest that expression of SCR 1 and 2 of EBVR/CR2 may be associated with replication of EBV and support the notion of direct infection and transformation of human nasopharyngeal epithelial cells destined to evolve into the carcinoma by EBV through EBVR/CR2.

Base Sequence↗
PubMed1998

Alpha-1 antitrypsin up-regulates human B cell differentiation selectively into IgE- and IgG4- secreting cells.

Numerous allergens have proteolytic activities. It has been speculated that this property may contribute to their allergenicity. Therefore, we have evaluated the effect of different physiological protease inhibitors (PI) on the regulation of human IgE synthesis. Unexpectedly, the serine PI, alpha-1 antitrypsin, also called alpha-1 protease inhibitor (alpha1PI), induced a potent and selective dose-dependent increase of IgE and IgG4 production by human tonsillar B cells stimulated with the IgE and IgG4 switch factors, IL-4 and anti-CD40 mAb. The other serine PI tested were inefficient. Furthermore, this effect of alpha1PI was accompanied by an increase in (1) germ-line and mature sigma mRNA transcription, (2) proliferation and (3) membrane CD23 and CD21 expression, while the expression of other molecules involved in the regulation of IgE synthesis was unchanged. Since CD23-CD21 pairing plays a crucial role in the up-regulation of IgE synthesis, we have tested whether blocking this interaction affected alpha1PI-increased IgE production. The neutralizing anti-CD23 mAb, Mab 25, partly reversed the IgE increase caused by alpha1PI. Moreover, alpha1PI potentiation of IgE synthesis was prevented by elastase, a natural substrate of alpha1PI, thereby suggesting that alpha1PI may inhibit endogenous B cell enzyme(s) involved in the down-regulation of IgE synthesis. Alpha1PI also potentiated IgE and IgG4 production by IL-4-stimulated peripheral blood mononuclear cells but was not a switch factor for IgE and IgG4 as it was unable to replace IL-4 or anti-CD40 mAb in inducing IgE and IgG4 production. In conclusion, this study shows that alpha1PI acts as a potent co-stimulus for IgE and IgG4 synthesis and suggests that the equilibrium between protease/ protease inhibitor participates in the control of human IgE and IgG4 synthesis.

Antibodies, Monoclonal↗
PubMed1998

CD72-mediated B cell activation involves recruitment of CD19 and activation of phosphatidylinositol 3-kinase.

Occupancy of the B cell glycoprotein, CD72 results in syk-independent activation of phospholipase-C gamma and calcium mobilization. The cytoplasmic tail of CD72 does not contain an immunoreceptor tyrosine-based activation motif to directly transduce signals into the B lymphocyte. Hence, we investigated whether other coreceptors such as CD19 and its associated phosphatidylinositol 3-kinase (PI 3-K) were involved in CD72 signaling. Two specific inhibitors of PI 3-K inhibited CD72-stimulated B cell proliferation in a dose-dependent manner. Activation of B lymphocytes via CD72 resulted in recruitment and activation of PI 3-K, which was mediated by CD19. Accordingly, CD72 ligation induced CD19 tyrosine phosphorylation. Thus, lipid products generated as a result of PI 3-K activation may have an important function in CD72-mediated B lymphocyte activation. The kinetics of CD19 tyrosine phosphorylation induced by CD72 ligation were strikingly different from those seen following B cell antigen receptor (BCR) stimulation. A transient increase in the tyrosine phosphorylation of the complement receptors, CD21 and CD35 was observed in BCR- but not CD72-stimulated cells. Co-cross-linking of CD72 and CD19 failed to induce syk tyrosine phosphorylation suggesting that even under these conditions, CD72 signaling was independent of syk activation. A transient and stimulation-dependent physical association between CD19 and CD72 was observed in CD72-ligated cells. These observations suggest a mechanism by which CD72 can recruit CD19 and influence activation of CD19-associated PI 3-K, which appears to be critical for CD72-mediated B cell activation.

Androstadienes↗
PubMed1998

Soluble CD21 induces activation and differentiation of human monocytes through binding to membrane CD23.

Interactions between CD23, the low-affinity receptor for IgE, and CD21, the C3d/EBV receptor, modulate several intracellular events in lymphocytes. A soluble form of CD21 (sCD21) corresponding to the extracellular domain of the receptor circulates in normal plasma. We now demonstrate that purified sCD21 acts as a functional ligand for CD23-expressing monocytes. Soluble CD21 induced an increase in intracellular cGMP levels and the production of IL-6 and TNF-alpha in IL-4-pretreated monocytes induced to express CD23 but not in unstimulated CD23- monocytes. The accumulation of cGMP and the production of TNF-alpha were inhibited by NG-monomethyl-L-arginine (L-NMMA), indicating that sCD21 activates the L-arginine pathway of NO production. We demonstrated that sCD21 activates NO synthase (NOS) since it was found to enhance the conversion of L-arginine into L-citrulline and induce the intracellular expression of inducible NOS in CD23+ monocytes. In addition, sCD21 was shown to up-regulate the expression of HLA-DR and CD40 and decrease that of CD14 on cultured CD23+ monocytes. Thus, in a fashion similar to IgE complexes, sCD21 is able to efficiently trigger CD23 signaling pathways, inducing the release of pro-inflammatory mediators by human monocytes. Soluble CD21 up-regulates the expression of molecules involved in antigen presentation, further suggesting a potential immunoregulatory function for the soluble molecule.

Antigen Presentation↗
PubMed1999

CD1high B cells: a population of mixed origin.

A specialized subpopulation of T lymphocytes is reactive to the MHC class I-like molecule CD1d. It is not clear which cells are the major antigen-presenting cells in vivo in the activation of CD1-restricted immune responses. We have characterized a subset of B lymphocytes expressing six- to eightfold higher levels of CD1 than the bulk of B cells. The cells have a surface phenotype (CD21(high), CD23(low), IgM(high), IgD(low)) found previously to characterize B cells residing in the splenic marginal zones. CD1(high) B cells localize preferentially to the spleen, and appear late in ontogeny, at 3 - 4 weeks of age. The CD1(high) B cells were present in mice lacking conventional helper T cells, ruling out an exclusive origin from T cell-dependent immune responses. Still, some CD1(high) B cells had been involved in T cell-dependent immune responses as suggested by mutations in their rearranged immunoglobulin gene regions. The population could still be found in mice with severely reduced B cell reactivity to bacterial lipopplysaccharides (C3H / HeJ mice) and in mice unable to respond to thymus-independent type 2 antigens (NFR.Xid mice), as well as in germ-free mice, indicating that bacterial antigens are not major stimuli for the induction of CD1(high) B cells. In contrast, the CD1(high) B cell population was severely reduced in CD19-deficient mice. Taken together, the results imply that the CD1(high) population is heterogenous and of mixed origin, dependent for its development or maintenance on signaling through the CD19 molecule.

Animals↗
PubMed2002

Age-related depression of FDC accessory functions and CD21 ligand-mediated repair of co-stimulation.

Morphological and kinetic studies of immune complex (IC) trapping by follicular dendritic cells (FDC) show marked age-related deficits. We postulated that a reduction in trapped IC, which generate CD21 ligands (L) on FDC, would lead to inadequate FDC-Ag-B cell interactions resulting in depressed Ab responses. To determine whether the age-related defect was the result of the aging of FDC or changes in the in vivo microenvironment of FDC (i.e. aging B and T cells), FDC-B cell-T cell-Ag interactions were studied in in vitro germinal centers where various combinations of old and young cells could be compared. Since we reasoned that reduced IC on FDC would generate less CD21L needed to stimulate the B cell co-receptor via CD21, we also examined the role of complement (C'). The hypothesis that aging reduces the accessory activity of FDC was tested with increasing numbers of FDC from young (12 weeks) or old (20 months) mice in the presence of young (12 weeks) B and T lymphocytes. The Ag-specific stimulatory activity of FDC was studied using the OVA-specific Ab response which was reduced by 40-50% in the presence of old FDC. Antigen-independent FDC-mediated co-stimulation was studied by using LPS to stimulate B-lymphocytes to produce immunoglobulin (Ig). In the presence of old FDC, co-stimulation was decreased by 70-80% in the LPS system. Incubation of aged FDC with IC and C' to provide FDC with CD21L restored co-stimulatory activity to near normal levels. In marked contrast, no defects in old B and T cells were apparent. The data suggest that the Ag handling capacity and co-stimulatory activity of old FDC become defective with aging and this appears to be a consequence of reduced trapping and presentation FDC-Ag and CD21L to B cells.

Aging↗
PubMed2002

Transmission of antibody-induced arthritis is independent of complement component 4 (C4) and the complement receptors 1 and 2 (CD21/35).

The K/BxN murine model of rheumatoid arthritis (RA) is dependent on the specificity of the KRN alpha beta-TCR, to recognize glucose-6-phosphate-isomerase (GPI) on the NOD MHC class II A(g7) allele and production of GPI-specific autoantibodies. Transfer of K/BxN serum into MHC-unrelated and lymphocyte-deficient mice induces RA. To investigate whether K/BxN serum-induced RA involves complement activation and/or the complement receptors (CR) 1 and 2, we analyzed the role of complement C4 and of CR1 and CR2. For this purpose we used C4(-/-) mice impaired in the classical and the lectin complement pathways; Cr2(-/-) mice lacking CR1 and CR2 and, as control strains, BALB/c, C57BL/6, KRN and NOD. RA was assessed by caliper measurement of ankle thickness, clinical index and joint histology. We found that all mouse strains except NOD developed RA. The lack of protection in C4(-/-) mice suggests that antibody-mediated RA is independent of the classical as well as the lectin complement pathways and the split complement product C4b. The lack of protection in Cr2(-/-) mice suggests that absence of CR1 had no significant affect, considering its role in immune complex clearance, inhibition of C3 and C5 convertase and as receptor for C3b/C4b. Also, CR2 lacks a role in disease as analyzed here, in its possible functions as receptor for C3dg, germinal center reaction and activation of alternative pathway on binding iC3. Hence we conclude that the transmission of K/BxN serum-induced RA is independent of the classical and the lectin complement pathways and CR1 and CR2. The crucial role of complement C5, while neither classical nor lectin pathway is necessary, indicates that the alternative complement pathway may have a role in the K/BxN serum-induced RA model.

Animals↗
PubMed1986

Autoantibodies against gp140, the Epstein-Barr virus and C3d receptor in sera from rheumatoid arthritis patients.

gp140 is the Epstein-Barr virus receptor and the C3d receptor (EBVR/C3dR) of human B lymphocytes. Recently, we have shown that cross-linking of EBVR/C3dR on cell surface by polyclonal anti-gp140 induced B cell activation, in presence of T cell factors. Immunoregulatory abnormalities of EBV-induced B cell activation have been demonstrated in rheumatoid arthritis (RA) patients. These data prompted us to analyze the putative presence of anti-EBVR/C3dR autoantibodies in human sera. The IgG fractions from eleven RA and 10 normal sera were tested for their ability to: (a) bind to Raji cell surface; (b) inhibit the binding to cell surface of 3 anti-EBVR/C3dR monoclonal antibodies (mAb), which recognized different epitopes on gp140; (c) inhibit the binding of particle-bound C3d and (d) react with 1% Nonidet-P40-solubilized gp140 from Raji cell membranes, in immunoblotting assays. Three RA sera carry anti-EBVR/C3dR autoantibodies which react with gp140 expressed on Raji cell surface or its solubilized form. The purification of monomeric IgG fraction of selected RA sera ruled out involvement of immune complexes carrying C3 molecules, which could interfere in these assays. One of these 3 RA sera was able to inhibit the binding to cell surface of anti-EBVR/C3dR mAb and particle-bound C3d. However, the 2 other RA sera, found positive by immunoblotting, did not inhibit particle-bound C3d and presented differences in their inhibitory effect on anti-EBVR/C3dR mAb binding to Raji cell surface. These data allow us to demonstrate differences which exist in the properties of anti-EBVR/C3dR autoantibodies. These autoantibodies were not detected in all the normal and other RA sera. Anti-EBVR/C3dR autoantibodies could play a role "in vivo" in B lymphocyte activation of RA patients.

Arthritis, Rheumatoid↗
PubMed1987

Activation of B lymphocytes by Epstein-Barr virus/CR2 receptor interaction.

Epstein-Barr virus (EBV) infects and transforms human B lymphocytes. The virus receptor was shown to be identical to the complement receptor CR2. The consequences of EBV/CR2 receptor interaction on B lymphocyte activation were analyzed by infection of B cells with the transforming (B95-8) and the nontransforming (P3HR1) virus strains and with UV-inactivated B95-8 virus. Similar to mitogens and antibodies against surface IgM and CR2 receptor, transforming and nontransforming EBV induced the release of leukocyte migration inhibitory factor (LIF). LIF production occurred early after infection and was not affected by irradiation of the B95-8 virus with doses of UV-light which prevented the expression of viral functions. B lymphocytes infected with UV-inactivated virus responded to T cell-derived B cell growth factors. The results demonstrate that binding of EBV to the CR2 receptor activates the B cells. Progression of the infected cells in the activation pathway required helper cell-derived factors or signals provided by the intact viral genome. The nontransforming P3HR1 virus induced a low level of RNA synthesis and increase of cell size and major histocompatibility complex class I antigen expression. Only the transforming virus induced expression of EBV nuclear antigens and cellular DNA synthesis.

Antibodies↗
PubMed1987

gp140, the EBV/C3d receptor (CR2) of human B lymphocytes, is involved in cell-free phosphorylation of p120, a nuclear ribonucleoprotein.

gp140, the EB/C3d receptor (EBV/C3dR; CR2), is a membrane site involved in human B cell regulation. Cross-linking of this receptor on the cell surface by its specific ligands led to the enhancement of B cell proliferation in synergy with T cell factors. In vitro activation of human peripheral B lymphocytes by cross-linking membrane immunoglobulins with anti-mu antibody induced EBV/C3dR phosphorylation. These studies were pursued by analyzing cell-free phosphorylation of EBV/C3dR isolated from Raji cell fractions, and immobilized on OKB7, a monoclonal anti-EBV/C3dR antibody. Three EBV/C3dR-related antigens which could be cell-free phosphorylated were detected: gp140, the EBV/C3dR, p130 and p120. gp140, the mature form of EBV/C3dR, was isolated from plasma membrane and from purified nuclei. p130 was identified as an intracellular intermediate of EBV/C3dR glycosylation, localized in low-density microsomes. Phosphoamino acid analysis of EBV/C3dR allowed the detection of phosphotyrosine and phosphoserine residues. These data suggest that EBV/C3dR could carry an autophosphorylation activity and could be associated to serine kinases. Using polyclonal anti-p120 antibody and anti-120 kDa nuclear ribonucleoprotein monoclonal antibody (mAb), p120 was identified as a nuclear ribonucleoprotein antigenically not related to EBV/C3dR. Detection of p120 on EBV/C3dR, immobilized on OKB7, was due to interactions between both antigens, instead of anti-EBV/C3dR mAb cross-reactivity with p120. Cell-free phosphorylation of p120 was under the control of EBV/C3dR. However, it is not yet established whether other nuclear or membrane components were involved in the control of p120 cell-free phosphorylation by EBV/C3dR. From the data presented herein, we propose that phosphorylation of a 120-kDa nuclear ribonucleoprotein by EBV/C3dR-associated kinases could represent a crucial step in in vivo regulation of human B cell activation.

B-Lymphocytes↗
PubMed1990

Stable expression and function of EBV/C3d receptor following genomic transfection into murine fibroblast L cells.

The Epstein-Barr virus (EBV) and the C3d component of complement bind to the same cell surface receptor (EBVR/CR2) which is part of the B lymphocyte differentiation antigen recognized by the monoclonal antibodies (mAb) of the cluster of differentiation 21 (CD21). To analyze EBV and C3d binding to this receptor, mouse fibroblasts were transfected with human genomic DNA and rare CD21-positive cells were selected and cloned by cell sorting. The presence of the human gene in host cell DNA as well as its transcription product were assayed with a cloned EBVR/CR2 cDNA by Southern and Northern blotting analysis, respectively. A glycoprotein of apparent molecular mass of 140 kDa, similar to that found in human B lymphocytes, was immunoprecipitated with anti-CD21 mAb and proved to be functional since both C3d and EBV bound efficiently and specifically to mouse cells expressing EBVR/CR2. However, no expression of EBV nuclear antigens, early antigens and viral capsid antigens was detected in cells exposed to EBV. This indicates that the presence of EBVR/CR2 is not sufficient to allow full infection of mouse fibroblasts.

Animals↗
PubMed1993

CD23 and CD21 function as adhesion molecules in homotypic aggregation of human B lymphocytes.

We have previously found that interleukin-4 and CD40 monoclonal antibodies (mAb) are strong potentiators of homotypic B cell aggregation which is dependent on LFA-1. We show here that CD23 mAb were also able to inhibit aggregation to a similar extent as LFA-1 antibodies. This inhibition was restricted to the MHM6 epitope of CD23 and antibodies to other epitopes [Epstein-Barr virus (EBV) CS-1, EBV CS-2, EBV CS-5 and mAb 25] or occupation of the Fc-binding site by IgE had no or a slightly enhancing effect on aggregation. When testing two antibodies to CD21, the recently defined ligand for CD23, one of these (BU32) was found to be inhibitory whereas the other (THB5) had no effect. By combining antibodies to LFA-1 and CD23, aggregation was often completely inhibited. These data suggest that LFA-1/ICAM-1 and CD23/CD21 are the major molecules involved in homotypic aggregation of human B cells.

Antibodies, Monoclonal↗
PubMed1993

CD21 expressed on basophilic cells is involved in histamine release triggered by CD23 and anti-CD21 antibodies.

Recombinant full-length human CD23 incorporated into fluorescent liposomes was used to detect a ligand for CD23 on the basophilic leukemia cell line, KU 812. Based on our recent finding that CD23 interacts with CD21 on subsets of B and T cells, we investigated if the same ligand was involved on KU 812 cells. An anti-CD21 monoclonal antibody (mAb) BU-33, was able to totally block CD23-liposome binding to KU 812 cells. Moreover, KU 812 cells express CD21 mRNA and have a cell surface molecule that reacts with anti-CD21 mAb. The CD23/CD21 interaction was not merely physical but was also associated with an increase in histamine release by KU 812 cells. Both recombinant soluble CD23 and an anti-CD21 mAb-mediated effect on histamine release was not restricted to and anti-CD21 mAb-mediated effect on histamine release was not restricted to the leukemic cell line, but was also observed with normal human blood basophils. These data demonstrate that CD21 is expressed on basophilic cells and that CD21 controls histamine production upon ligand-induced stimulation (CD23 or anti-CD21 mAb).

Antibodies, Monoclonal↗
PubMed1994

Allergen-induced CD23 on CD4+ T lymphocytes and CD21 on B lymphocytes in patients with allergic asthma: evidence and regulation.

Interaction of CD4+ T cells and B cells is necessary for IgE production. It has been recently demonstrated that cell surface antigen CD21 is a ligand for CD23 (Fc epsilon RII) and that the pairing of these molecules may participate in the control of IgE production. In this study we investigated the effect of the Dermatophagoides pteronyssinus (Dpt) allergen and recombinant interleukin(rIL)-4 on the expression of CD21 and CD23 on T and B cells of asthmatic patients allergic to Dpt and of healthy controls. Peripheral blood mononuclear cells (PBMC) were incubated alone or with Dpt allergen (100 biological units/ml) and/or rIL-4 (100 U/ml) for up to 7 days. The flow-cytometric analysis of double-fluorescence staining revealed that Dpt allergen and/or rIL-4 induced CD23 on CD4+ T lymphocytes only in allergic patients. The allergen-induced CD23 on T cells is de novo synthesized antigen since no induction of CD23 on T cells was observed in cultures with 0.4 microgram/ml actinomycin D. Moreover, 100 U/ml of interferon-gamma inhibited the induction of CD23 on CD4+ T cells. T cells obtained from healthy donors did not express CD23 or CD21 antigen upon incubation with allergen and/or rIL-4. Although rIL-4 also induced CD23 in controls, the expression was only observed on CD20+ cells. The allergen alone induced a significant elevation of the mean fluorescence intensity of both CD21 and CD23 only in allergic individuals. When the cell proliferation was analyzed, a slightly increased stimulation index upon cultivation of PBMC was obtained from non-allergic donors as well, but less than in allergic patients. The co-expression of major histocompatibility complex class II molecules and CD23 on CD4+ T lymphocytes in allergic patients, as assessed by the three-color immunofluorescence analysis, indicates that these cells were activated. We conclude that CD4+ T lymphocytes possess a unique capability to express CD23 upon exposure to allergen. Moreover, the allergen-mediated induction of CD23 on T cells observed only in allergic patients may be the reason for the increase of IgE production. This would not occur in non-allergic individuals as there is no CD23 expression on T cells.

Adult↗
PubMed1994

CD23/CD21 interaction is required for presentation of soluble protein antigen by lymphoblastoid B cell lines to specific CD4+ T cell clones.

Previous studies have documented a role for membrane-bound CD23 (the low affinity Fc epsilon RII) in presentation of alloantigens by B cells. The aim of the present study was to examine the involvement of cell surface CD23 in presentation of more conventional soluble protein antigens to T cells. We show that antibodies to CD23 and to its lymphocyte-associated second ligand, CD21, inhibit presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B-EBV cell lines to casein-specific HLA-DP-restricted CD4+ T cell clones obtained from patients with either reaginic or enterophatic forms of cow's milk protein intolerance. Maximal inhibition was achieved when the antibodies were added at the initiation of the culture. The absence of specific inhibition by an anti-DR alpha monoclonal antibody (mAb) argues against a steric hindrance phenomenon impeding access of the T cell receptor to major histocompatibility complex class II molecules. Rather, anti-CD23 and anti-CD21 mAb-induced inhibition of antigen presentation seems to affect at least partly, heterotypic conjugate formation through CD23/CD21 interaction. Double immunofluorescence labeling of the T cell clones and antibody inhibition of T/B conjugate formation shows that functional CD23 and CD21 molecules are induced on T cells following contact with B-EBV cell lines. Taken together, these data indicate that CD23/CD21 interactions between T and B cells are required for presentation of soluble protein antigens by B-EBV cell lines to specific CD4+ T cells. The potential implications of these findings for allergen-specific T cell activation are discussed.

Antigen-Presenting Cells↗
PubMed1995

Epstein-Barr virus/C3d receptor (CR2, CD21) activated by its extracellular ligands regulates pp105 phosphorylation through two distinct pathways.

We previously demonstrated that human C3d or pep16, a 16-amino acid synthetic peptide derived from human C3d, induced in vivo and in vitro tyrosine phosphorylation of pp105, an intracellular component found only in human cells that express CR2 at their surface. To determine the contribution of CR2 molecules to this enzymatic regulation, we first analyzed whether activation of CR2 by other extracellular CR2 ligands could trigger such regulation in cell extracts. Subsequently, we used cell extracts of either CR2-positive cells depleted in CR2 molecules by absorption with anti-CR2 antibodies or CR2-negative cells transfected with CR2 cDNA. We demonstrate here that pp105 phosphorylation was induced when CR2 was activated by C3d and pep16 as well as by gp350, the Epstein-Barr virus capsid protein or OKB7, an anti-CR2 monoclonal antibody (mAb). HB5, another anti-CR2 mAb, which did not activate B lymphocytes through CR2, did not induce pp105 phosphorylation. Thus, C3d, pep16, gp350, and OKB7 presented similar properties in activating CR2 to trigger pp105 phosphorylation and in regulating B lymphocyte proliferation, while HB-5 had no effect on either assays. Furthermore, our data demonstrate that the presence of CR2 activated by its extracellular ligands regulates pp105 phosphorylation through two distinct pathways: one which also requires the presence of non-activated CD19, and one which is independent of CD19. The involvement of CD19 in the first pathway was not due to the formation of putative CR2-CD19 complexes. Both pathways were TAPA-1 independent. This is the first demonstration that activated CR2 molecules can play a regulatory role in enzymatic function, such as phosphorylation, despite the absence of CD19 and TAPA-1.

B-Lymphocytes↗
PubMed1996

Human lymphocytes shed a soluble form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that binds iC3b and CD23.

We report on a soluble (s) form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that is spontaneously released by B and T lymphocytes. Immunoprecipitation with anti-CD21 mAb of culture supernatants of surface and biosynthetically labeled B and T cell lines revealed a single band with an apparent molecular mass of 135 kDa. The molecule exhibited a molecular mass 10 kDa lower than that of membrane CD21. The release of soluble CD21 (sCD21) was time dependent and correlated with a parallel decrease in the expression of the membrane-associated molecule. The protein was also found in culture supernatants of tonsillar B cells and normal human thymocytes. Epitopic analysis using combinations of anti-CD21 monoclonal antibodies (mAb) indicated that sCD21 and membrane CD21 were similarly recognized by mAb directed against short consensus repeats (SCR) 1-2, SCR 4-5 and SCR 9-11. Affinity-purified sCD21 was capable of binding to purified human iC3b and to human recombinant CD23, as assessed by enzyme-linked immunosorbent assay and by using the BIAcore technology. In addition, normal human serum was found to contain a soluble form of CD21 that exhibited a similar molecular mass to that of the molecule shed by B and T cells in culture. The serum form of CD21 was recognized by all anti-CD21 mAb that we tested and showed a high reactivity with mAb directed against SCR 1-2. Our observations suggest that B and T cells shed the extracellular portion of CD21 and release a soluble molecule that retains the ligand-binding properties of CD21, thus having a potential role in immunoregulation.

B-Lymphocytes↗
PubMed1997

Cleavage of the low-affinity receptor for human IgE (CD23) by a mite cysteine protease: nature of the cleaved fragment in relation to the structure and function of CD23.

Der p I, a cysteine protease representing a major allergen of the house dust mite Dermatophagoides pteronyssinus, has recently been shown to cleave CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). We have now undertaken a detailed investigation of CD23 cleavage by Der p I. We demonstrate that Der p I cleaves CD23 at two sites (Ser155-Ser156 and Glu298-Ser299) to produce a 17-kDa fragment containing the lectin domain and only part of the C-terminal tail. No such effect was demonstrable with mouse CD23, a finding which was anticipated based on its lack of the cleavage sites identified on human CD23. Based on the cleavage pattern and the model of CD23, we propose a sequence of events leading to the liberation of the 17-kDa soluble CD23 fragment. The biological significance of such cleavage is underlined by the demonstration that Der p I-treated B lymphocytes lose their ability to bind IgE, and that the 17-kDa fragment (amino acids 156-298) contains the minimum structural requirement (amino acids 156-288) for binding to both IgE and CD21.

Animals↗