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PubMed1985

Neutrophils express a receptor for iC3b, C3dg, and C3d that is distinct from CR1, CR2, and CR3.

In the present study we examined human neutrophils for the expression of a receptor capable of binding C3dg and defined the relationship of this receptor to those that have been previously described, namely CR1, CR2, and CR3. C3dg was isolated from serum depleted of plasminogen, supplemented with 20 mM Mg++, and incubated at 37 degrees C for 6 to 8 days. The purified protein was homogeneous when analyzed by polyacrylamide gel electrophoresis and exhibited an apparent m.w. of 41,000. C3dg was polymerized by treatment with dimethyl suberimidate, and the dimer was isolated by gel filtration. Binding of both monomeric and dimeric 125I-labeled C3dg to neutrophils was saturable, and the latter ligand bound to an average of 12,400 sites/cell among nine normal individuals. At 4 degrees C, bound monomeric C3dg dissociated from neutrophils with an average t1/2 of 30 min, whereas dimeric C3dg dissociated with a t1/2 in excess of 120 min. Specific binding of multimeric C3dg was cation independent and was competitively inhibited by molar concentrations of iC3b and C3d that were equivalent to the inhibitory concentrations of unlabeled C3dg; C3b was less able to compete with C3dg for binding to these sites. The capacity of this neutrophil receptor to bind iC3b, C3dg, and C3d suggested its possible identity as CR2 or CR3. However, no specific binding to neutrophils of 125I-labeled HB-5 monoclonal anti-CR2 was detected. Furthermore, uptake of 125I-labeled C3dg was not inhibited by saturating concentrations of rabbit anti-CR1, anti-Mac-1, or OKM10. Thus, a receptor resides on neutrophils that binds the C3d region of iC3b and C3dg and is distinct from CR1, CR2, and CR3.

Animals↗
PubMed1983

C3 receptors on human lymphocyte subsets and recruitment of ADCC effector cells by C3 fragments.

The presence of C3 receptors on human peripheral blood lymphocytes (PBL) and on the ADCC-exhibiting subset (K cells) thereof was analyzed by rosetting with bovine erythrocytes (Eb) or chicken erythrocytes (Ec) carrying human C3b, C3bi, or C3d. The indicator cells were coated with 20,000 to 100,000 C3 fragments, obtained by C3 activation with purified proteins of the alternative pathway and trypsin treatment. ADCC was studied at the cellular level by means of a plaque assay, with complement-free or complement-carrying indicator cells as targets. Of the total lymphocytes, 12 to 14% bound EC3b; 6 to 8%, EC3bi; and approximately 2%, EC3d. Surface marker analysis indicated that approximately 75% of the C3b-binding lymphocytes in PBL were either B or null cells and approximately 60% of the C3bi-binding cells were T cells, as characterized by the monoclonal antibodies OKT3 and OKT4 or by presence of receptors for Helix pomatia hemagglutinin. Of the K cells, which constituted from 5 to 10% of the total lymphocytes, approximately 20% bound C3b; 30 to 35%, C3bi; and 7 to 8%, C3d. Here the majority of the C3b binders were null cells, and the majority of the C3bi and C3d binders were T cells. Only one-third of the C3b-binding K cells and one-fifth of the C3bi-binding K cells bound both fragments. The nature of these double binding cells is unknown. In contrast, all C3d-binding K cells bound C3bi as well. C3 fragment-carrying target cells did not induce K cell-mediated lysis in the absence of anti-target antibodies but strongly enhanced ADCC in the presence of sublytic concentrations of such antibodies. The rank order for C3 fragment-induced enhancement was C3bi greater than C3d greater than C3b. It reflected the relative proportions of effector cells binding the different fragments. Enhancement was the expression of effector cell recruitment rather than of increased cytolytic activity of individual K cells. This recruitment was selective in that C3b-carrying target cells primarily recruited effector cells of null type, binding C3b, while C3bi- or C3d-carrying targets primarily recruited C3bi and/or C3d-binding K cells of T gamma type. Thus, these experiments show directly at the effector cell level that cell-bound C3 fragments constitute important recognition structures, which strongly amplify ADCC both by recruiting the proper effector cells into the cytolytic reaction and by very significantly decreasing the antibody concentration needed for its induction.

Animals↗
PubMed1984

Expression of C3d receptors during human B cell differentiation: immunofluorescence analysis with the HB-5 monoclonal antibody.

We have examined human B lymphocytes at different stages of differentiation for the expression of surface receptors for the C3d fragment of complement. C3d receptors (C3dR) were identified by indirect immunofluorescence using the HB-5 monoclonal antibody, which recognizes a 145,000 m.w. C3dR molecule on B lymphocytes. Pre-B and immature B cells from fetal bone marrow and liver did not express C3dR, whereas a small subpopulation (25%) of B cells in fetal spleen were C3dR+. Approximately 50% of the B cells in adult bone marrow were C3dR+, whereas the more mature B cells in the blood of newborns and adults and in peripheral lymphoid tissue of adults uniformly expressed the C3dR. Activated B cells responsive to T cell-derived differentiation factors were C3dR+, whereas plasma cells rarely expressed C3dR. T cells, NK cells, erythrocytes, and myelomonocytic cells did not express detectable surface C3dR. These results suggest that in hematopoietic and lymphoid tissues, the expression of C3dR is a specific feature of relatively mature lymphoid cells of B lineage.

Adult↗
PubMed1994

CR2 is the primary acceptor site for C3 during alternative pathway activation of complement on human peripheral B lymphocytes.

Human cells infected with certain viruses acquire the ability to activate the alternative pathway (AP) of complement. Complement receptor 2 on EBV-infected lymphoblastoid cell lines has been reported to act as the covalent binding site for C3b during AP activation. Using flow cytometry, we investigated the ability of normal human peripheral blood leukocytes to activate the AP in homologous serum. Deposition of C3 fragments was determined as a measurement of complement activation on each of the subpopulations of the blood cells. Incubating human peripheral blood leukocytes with homologous or autologous serum resulted in C3 deposition on B cells and, to a lesser extent, on monocytes and polymorphonuclear leukocytes. Complement activation in the presence of Mg2+ ions and EGTA revealed major involvement of the AP in the case of B cells, and to a lesser extent for other leukocyte populations examined. Preincubation of the leukocytes with polyclonal anti-complement receptor 2 Ab markedly decreased the C3 fragment deposition, as a result of in vitro AP activation, on B cells, indicating that on normal human B cells this receptor may be involved in AP activation. Freshly isolated, normal human B cells also bear low but significant amounts of C3d,g fragments on their membranes, indicating that this AP activation also occurs in vivo. AP activation was partially decreased in the presence of autologous erythrocytes (RBC) suggesting that complement regulatory proteins on RBC play a role in limiting the AP activation in vivo.

Antigens, CD↗
PubMed1994

Antigen receptor-mediated transmembrane signaling in Wiskott-Aldrich syndrome.

The X-linked immunodeficiency Wiskott-Aldrich syndrome (WAS) is a condition that includes a deficient anti-polysaccharide Ab response. Recently, it has been suggested that B cells from patients with WAS show a defective calcium mobilization response upon engagement of sIgM. Because primarily EBV-transformed cells were used in these studies, we tested freshly isolated blood B cells for their calcium mobilization capability upon engagement of sIg and CD19. No significant differences in the calcium mobilization capability of CD20+ B cells of four individual WAS patients compared with capability in normal controls were found. Receptor desensitization as assessed by calcium mobilization inhibition also seemed to be intact. T cells were tested for their anti-CD3-induced calcium flux and, again, no abnormalities could be observed when compared with T cells from healthy individuals. We conclude that WAS B and T cells can be stimulated into a normal calcium mobilization response when their AgRs are cross-linked. It is highly improbable that the immune dysfunction observed in WAS patients is related to a direct disorder of their B and/or T cell AgRs.

Adolescent↗
PubMed1994

Modulation of signaling via the B cell antigen receptor by CD21, the receptor for C3dg and EBV.

CD21 is the receptor for C3dg and EBV. Several reports have shown that these CD21 ligands, and certain anti-CD21 mAb, trigger B cell activation, particularly when combined with Ag receptor ligation. However, the characteristics, biologic functions, and importance of this CD21-signaling pathway are unknown. We have used a model we recently developed to study B cell activation induced by complex particulate Ag, such as immune complexes and viruses, to begin to examine these questions. In the current studies, we incubated purified small resting B cells with 100-nm latex beads bearing various combinations of CD21 ligands and mAbs to CD19, CD35, and the Ag receptor. CD21, CD19, and CD35 have all been implicated in modulating membrane IgM initiated signaling. Beads coated with mAb to the C3dg/EBV-binding portion of CD21, but not mAb to other portions of the CD21 molecule, triggered B cell homotypic aggregation. Beads coated with the same CD21 ligands, although inactive alone, synergized with anti-IgM mAb in greatly increasing (20- to 180-fold) mRNA levels of the c-fos nuclear proto-oncogene. Signaling via CD21 was tyrosine kinase dependent. Levels of c-myc mRNA were not altered by CD21 ligands. Anti-CD19 and anti-CD35 mAb did not augment signaling via membrane IgM as assessed by changes in c-fos mRNA levels. These findings indicate that CD21 ligands binding to the C3dg/EBV-binding site of CD21 markedly augment B cell activation initiated by Ag receptor ligation via a selective, c-fos-dependent signaling pathway.

Antibodies, Monoclonal↗
PubMed1995

Epstein-Barr virus modulates de novo protein synthesis in human neutrophils.

Neutrophils and macrophages represent the first line of defense against microbial invaders. However, the role of phagocytes in host response to viral infection is poorly understood. We have previously shown that Epstein-Barr virus (EBV) interacts with human monocytes and modulates cytokine production in this cell type, but its effects on neutrophils are still unknown. In the present study, we investigated the presence of EBV receptor (CR2 or CD21) on neutrophils by cytofluorometry using five different anti-CD21 monoclonal antibodies (MoAbs), as well as fluoroscein isothiocyanate-EBV (FITC-EBV). Whereas no significant amount of neutrophils reacted with anti-CD21 MoAbs, studies with FITC-EBV indicated that viral particles bind to 30% of cells (in some individuals, EBV binds to more than 50% of neutrophils). This interaction is specific as it was completely inhibited by nonconjugated virus or with labeled virus preincubated with neutralizing MoAbs. After EBV treatment, cellular aggregation was observed in neutrophil cultures, an indication that neutrophils were activated. Although EBV did not induce respiratory burst activity in neutrophils, pretreatment with infectious particles enhanced (priming effect) the fMLP-induced O2- release in neutrophils. Instead of restricting our analysis to specific cytokine genes, we investigated the effects of EBV on neutrophil transcriptional events in general. The effect of this virus on de novo synthesis of total cellular RNA was first investigated by measuring the incorporation of [5-3H] uridine into total RNA. The results showed that RNA synthesis in neutrophils was significantly increased (2.3- to 21.3-fold) by EBV compared with the unstimulated controls. Live and UV-inactivated virus markedly induced RNA synthesis, whereas heat-inactivated virus lost this ability. Induction of RNA transcription was EBV specific, as an EBV-neutralizing antiserum abolished this effect. Induction of protein synthesis was also studied by measuring the incorporation of [35S] methionine and [35S] cysteine into secreted and intracellular proteins in neutrophils incubated with EBV. The synthesis of both secreted and cytoplasmic proteins was induced by EBV. One- and two-dimensional gel electrophoresis analysis showed that EBV modulates protein synthesis, because activation of the synthesis of certain proteins was accompanied by the inhibition of others. Interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) synthesis was found to be induced by EBV. Therefore, modulation of host-response proteins such as IL-1Ra could be one of the many mechanisms by which this virus avoids rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1995

Characterization of rat complement receptors and regulatory proteins. CR2 and Crry are conserved, and the C3b receptor of neutrophils and platelets is distinct from CR1.

In the mouse, CR1 and CR2 on B lymphocytes are encoded by alternatively spliced Cr2 gene transcripts. Immune adherence receptors that bind C3b are present on mouse platelets and unstimulated neutrophils, but they are not CR1. In this study, rabbit anti-mouse CR1/CR2 Ab immunoprecipitated a 145- to 150-kDa CR2 protein from rat platelets, neutrophils, and splenocytes, but not a approximately 200-kDa CR1 protein. By Northern analysis, cDNA for mouse CR2 hybridized to mRNA of 3.7 and 5.2 kb from both mouse and rat splenocytes. The murine decay-accelerating factor and membrane cofactor protein analogue Crry was present in rat platelets, neutrophils, E, and splenocytes as two distinct proteins of 65 to 70 kDa and 75 to 85 kDa. Rat platelets, neutrophils, and splenocytes contained a novel 200-kDa cell membrane protein that specifically bound to a rat C3b-Sepharose column. We have named this protein C3bR-200. C3bR-200 was not identified by anti-mouse CR1/CR2 or anti-human CR1 Ab. Rat E lacked C3bR-200. Rat neutrophils and splenocytes also contained an 80-kDa C3b-binding protein that was distinct from Crry, which we have named C3bR-80. Therefore, CR2 and Crry are present in the rat, and have similar qualities to those from the mouse, except that CR2 is located on rat platelets and neutrophils, which is not the case in the mouse. Rat platelets, neutrophils, and splenocytes have a 200-kDa C3b-binding protein, C3bR-200, that is likely to be the rodent immune adherence receptor.

Animals↗
PubMed1993

Cell type- and stage-specific expression of the CD20/B1 antigen correlates with the activity of a diverged octamer DNA motif present in its promoter.

The CD20(B1) gene encodes a B cell-specific protein involved in the regulation of human B cell proliferation and differentiation. Studies with 5' deletion CD20 promoter-CAT constructs have previously revealed two regions of the promoter between bases -186 and -280 and between bases -280 and -454 which contained positive regulatory elements. In this study we identified a sequence element present in the most proximal region located between bases -214 and -201, TTCTTCTAATTAA, which is important in the high constitutive expression of CD20 in mature B cells and the induction of CD20 in pre-B cells. This sequence element was referred to as the BAT box and its deletion significantly reduced the activity of a CD20 promoter-CAT construct in B cells. Mobility shift assays with various mutant probes and B cell nuclear extracts demonstrated that the core sequence TAAT was essential for binding to this site. Cross competition experiments with an octamer sequence from the Ig heavy chain promoter, the BAT box, and a TA-rich sequence present in the CD21 promoter revealed that all three sequences bound the same nuclear proteins suggesting that the BAT box binding proteins were Oct-1 and Oct-2. Southwestern blotting and UV cross-linking studies confirmed that the BAT box binding proteins were Oct-1 and Oct-2. The affinity of the BAT box binding proteins for the BAT box was approximately 25-fold less than for the octamer sequence and the BAT box binding proteins dissociated from the BAT box 10-fold more rapidly than from the octamer sequence. Despite this lower affinity, a trimer of the BAT box sequence was as efficiently transactivated by an Oct-2 expression vector as was a trimer of the octamer sequence in HeLa cells. The BAT box and Oct-2 were also implicated in the induction of CD20 in the pre-B cell line, PB-697, via phorbol esters. The induction of CD20 mRNA was temporally associated with induction of Oct-2 mRNA and a BAT box-deleted CD20-CAT construct, in contrast to the wild type, was poorly induced by phorbol esters. Together these results suggest that the BAT box binding proteins are important in the B cell specific expression of CD20 and perhaps CD21.

Antigens, CD↗
PubMed1993

Analysis of the B-cell compartment in plasma cell leukemia and multiple myeloma: immunoglobulin gene rearrangement of EBV-infected B-cell lines.

Multiple myeloma (MM) is defined as a tumoral expansion of plasma cells occurring in the bone marrow and sometimes in the peripheral blood (plasma-cell leukemia, PCL). Many reports have demonstrated a clonal expansion of B cells bearing the same idiotypic determinants as the myeloma protein (idiotypic B cells) in MM, suggesting that they could belong to the malignant clone. In order to investigate whether the B-cell population is a malignant component or not, either in the peripheral blood of patients with PCL or in the bone marrow of patients with MM, we derived B-cell lines by infecting, with the Epstein-Barr virus (EBV), cultures in limiting dilution of mononuclear cells from six patients. A limiting dilution culture was used to prevent the elimination of slowly proliferating clones by the more rapidly dividing ones, and thus to get the most exact representation of the B-cell repertoire of these patients. The cloning efficiency of the EBV-infected cells was similar in patients and healthy individuals (range: 1 in 100 to 1 in 1650 B cells). All of the clones obtained from a single patient exhibited different clonal immunoglobulin gene rearrangements (IGR), proving the validity of our cloning technique. No tumoral clones (61 clones analysed) showed the IGR pattern specific of autologous myeloma cells. These results indicate that malignant plasma cells cannot be immortalized with EBV. These results show that, if malignant B cells (pre-switch or post-switch) exist, they could be present only in a minor population, and the corollary of this is that there is a major population of non-malignant B cells in the sites of tumoral proliferation of patients with MM. This is remarkable in view of numerous reports showing a profound defect of the polyclonal B lymphopoiesis in these patients, and even an absence of B lymphocytes. Thus, these results challenge the existence of a major compartment of malignant idiotypic B cells and favor the hypothesis of non-malignant B cells sharing cross-reactive idiotypes with the autologous myeloma protein.

Antigens, CD↗
PubMed1993

Regulation of survival in normal and neoplastic B lymphocytes.

The regulation of survival is clearly a vital component in deciding the fate of normal and malignant cells. In cell populations subject to selection through apoptosis, dysregulation of this mechanism could disrupt homeostasis with the potential overproduction of affected clones. Germinal centres are the sites of such selection for B cells proliferating in response to T-dependent antigen: two tumours arising at these sites--Burkitt lymphoma (BL) and follicular centre cell (FCC) lymphoma--show aberrations in their capacity to undergo programmed cell death (PCD). Here, we summarize present knowledge on the factors, both extra- and intracellular, which regulate survival in normal and malignant B cells arising in germinal centres.

Antigens, CD↗
PubMed1993

The CD19 signal transduction complex of B lymphocytes. Deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu 13.

CD19 expressed on the surface of B lymphocytes is a key member of a cell surface signal transduction complex that includes TAPA-1, Leu 13 and CD21. The human CD19 protein is composed of 540 amino acids with a cytoplasmic domain of 242 amino acids. Although the cytoplasmic domain of CD19 has no sequence homology with other proteins, the cytoplasmic domain of human, mouse, and guinea pig CD19 is highly conserved suggesting that this region of CD19 is at least partially responsible for signaling activity. In this study, the regions of CD19 required for intermolecular associations and signal transduction were determined by comparing a series of carboxyl-terminal cytoplasmic tail deletion mutants and a CD19/L-selectin chimera with native CD19. CD19 expressed in the human Rex T cell line and the K562 erythroleukemia cell line generated transmembrane signals and also associated with endogenous TAPA-1. Deletion of 95% of the CD19 cytoplasmic domain did not affect the ability of CD19 to be expressed or to associate with TAPA-1. However, replacement of the CD19 transmembrane and cytoplasmic domains with those of L-selectin (CD19-LAM) resulted in the loss of CD19 complex formation, suggesting that the membrane spanning domain is critical for this association. Similarly, the induction of homotypic adhesion through CD19 or truncated CD19 was equivalent, whereas homotypic adhesion was not induced via the CD19-LAM chimera. In addition, the cytoplasmic domain was not necessary for CD19 mAb-mediated growth inhibition or internalization. In contrast, the CD19 cytoplasmic domain was required for optimal mAb-induced increases in [Ca2+]i in CD19 cDNA-transfected Rex cells. Thus, the CD19 cytoplasmic domain is responsible for the induction of increased [Ca2+]i, and the transmembrane region is required for cell surface associations with the other members of the CD19 complex and most signaling events. Therefore, mAb binding to CD19 is likely to initiate multiple intracellular signal transduction cascades either through CD19 directly, or through other members of the CD19 complex.

Antigens, CD↗
PubMed1995

Comparison of the binding of C3S and C3F to complement receptors types 1, 2, and 3.

The two common polymorphic variants of C3 are C3S/HAV4.1- and C3F/HAV4.1+. It was reported previously that erythrocytes coated with C3F rosetted more strongly with mononuclear cells than erythrocytes coated with C3S. We examined the binding of C3S/HAV4.1- and C3F/HAV4.1+ to complement receptors CR1, CR2, and CR3. The binding of 125I-labeled C3b dimers to erythrocyte CR1 was measured. Scatchard analysis showed a two-binding constant model with very similar binding constants for dimers prepared with C3S and C3F: for C3S Kd1 = 18.3 +/- 2 nM; Kd2 = 6.2 +/- 1 nM; for C3F Kd1 = 21.5 +/- 4 nM; Kd2 = 7.2 +/- 3 nM (mean +/- SEM). One-third of the binding sites were of the higher affinity. The rosetting of erythrocytes with different densities of iC3b, prepared from C3S or C3F, to CR2 on Raji cells was analyzed. The percentage of Raji cells rosetted was related to the coating dose of EC3bi: 400 molecules/cell = 9% rosettes; 5000 molecules/cell = 75%. The dose-response curves were very similar for C3S- and C3F-coated erythrocytes. CR3-dependent rosetting was studied in a similar manner by using neutrophils activated with f-met-leu-phe. CR3-dependent rosette formation with the indicator erythrocytes (600 to 6000 iC3b/cell) increased from 10% to 60% in a dose-dependent manner and was closely similar for C3S and C3F. Inhibition of CR2 and CR3 rosetting by fluid phase ligand was also studied. iC3b dimers (0.4 to 50 micrograms/ml) inhibited CR2-dependent rosetting in a dose-dependent manner but had no inhibitory effect on CR3-dependent rosetting. When the dimers were absorbed to fluorescent microspheres, they mediated phagocytic uptake of the microspheres in a CR3-dependent manner by neutrophils. CR3-dependent binding by activated neutrophils required surface-bound ligand.

Complement C3↗
PubMed1995

Characterization of a complement receptor 2 (CR2, CD21) ligand binding site for C3. An initial model of ligand interaction with two linked short consensus repeat modules.

Human CR2 (CD21, EBV receptor) is an approximately 145-kDa receptor and a member of the regulators of complement activation gene family. Regulators of complement activation proteins are characterized by the presence of repeating motifs of 60 to 70 amino acids that are designated short consensus repeats (SCR). CR2 serves as a receptor for four distinct ligands. Three of these ligands (complement C3, gp350/220 of EBV, and CD23) interact with the amino terminal 2 of 16 SCR (SCR 1 and 2). Previous studies have determined that at least four sites are important in allowing CR2 to efficiently bind EBV. Two of these sites are also important for binding mAb OKB7, a reagent that blocks both EBV and iC3b/C3dg binding to CR2. We have identified and characterized important sites of iC3b ligand binding by utilizing human-mouse CR2 chimeras, a rat anti-mouse CR2 mAb designated 4E3 that blocks receptor binding to C3, and human CR2-derived peptides. In addition to demonstrating an important role for the same sequence in SCR 1 that is part of the mAb OKB7 and EBV binding site, we have identified a new region within SCR 2 that interacts with C3. These results, when compared with a model of a dual SCR solution structure derived from human factor H SCR, predict that two distinct largely surface-exposed sites on CR2 interact with iC3b. A relative twist of 130 degrees about the long axis of the second SCR in this model would be necessary for these sites to form a single patch for iC3b binding on CR2.

Amino Acid Sequence↗
PubMed1995

Antibodies to murine complement receptor 1 and 2 can inhibit the antibody response in vivo without inhibiting T helper cell induction.

Administration to mice of mAb against CR1/CR2 inhibits the primary and secondary in vivo Ab response. We have addressed the question of whether induction of T helper cells, in addition to B cells, is inhibited by this treatment. A hapten-carrier system was used, where one group of mice was immunized with a monoclonal CR1/CR2-specific Ab and Ag (SRBC or keyhole limpet hemocyanin (KLH)), another with Ag alone, and a third group left nonimmunized. After 2 to 15 wk, spleen cells from these mice were transferred to irradiated syngeneic recipients, together with Ag coupled to the hapten 4-hydroxy-5-iodo-3-nitro-phenacetyl (NIP). The number of NIP-specific, IgG-producing B cells, which in this system is an indication of T cell priming, was determined in an ELISPOT assay. Although the primary SRBC- or KLH-specific IgG response was inhibited markedly (74-98%) by CR1/CR2-specific Ab, no decrease in the number of NIP-specific IgG-producing B cells was detected after secondary immunization. In sharp contrast, the SRBC- or KLH-specific secondary IgG responses were low or undetectable. These findings suggest that CR1/CR2-specific Ab can inhibit the primary Ab response without affecting T helper cells and that the induction of B cell memory is decreased markedly by this treatment.

Animals↗
PubMed1995

Expression of CD21 antigen on myeloma cells and its involvement in their adhesion to bone marrow stromal cells.

The mature myeloma cells express very late antigen 5 (VLA-5) and MPC-1 antigens on their surface and adhere to bone marrow (BM) stromal cells more tightly than the VLA-5-MPC-1- immature myeloma cells in vitro. The VLA-5 and MPC-1 antigens possibly function as two of the molecules responsible for interaction of mature myeloma cells with BM stromal cells. However, the immature myeloma cells do interact with BM stromal cells, and it is unclear which adhesion molecules mediate their interaction. In this study, we found that both immature and mature myeloma cells expressed CD21, an adhesion molecule known to bind to CD23. CD21 was also detected on normal plasma cells. To evaluate the role of CD21 expression on myeloma cells, two myeloma cell lines, NOP-2 (VLA-5-MPC-1-) and KMS-5 (VLA-5+MPC-1+), were used as representatives of immature and mature myeloma cell types, respectively, and an adhesion assay was performed between the myeloma cell lines and BM stromal cells. Antibody-blocking results showed that adhesion of the mature type KMS-5 to KM102, a human BM-derived stromal cell line, or to short-term cultured BM primary stromal cells was inhibited by monoclonal antibodies (MoAbs) against CD21, VLA-5, and MPC-1, and inhibition of adhesion of the immature type NOP-2 to KM102 by the anti-CD21 MoAb was observed as well. Furthermore, CD23 was detected on KM102. Treatment of KM102 with an anti-CD23 MoAb also inhibited adhesion of either KMS-5 or NOP-2 to KM102. Therefore, we propose that CD21 expressed on myeloma cells likely functions as a molecule responsible for the interaction of immature myeloma cells as well as mature myeloma cells with BM stromal cells, and CD23 may be the ligand on the stromal cells for the CD21-mediated adhesion.

Base Sequence↗