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At least 19 recordsLinked to original sources
PubMed1988

Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein.

Two cDNA clones encoding the pan-B cell CD20 antigen were isolated from a COS cell expression library. The two clones bear identical coding sequences and differ only in the length of the 3' untranslated region. The predicted CD20 sequence is 297 residues long and contains three hydrophobic domains, one of which is long enough to span the membrane twice. COS cells transfected with either CD20 clone express an immunoreactive protein of 33 kD.

Amino Acid Sequence↗
PubMed2005

GM-CSF does not increase CD20 antigen expression on chronic lymphocytic leukemia lymphocytes.

CD20 antigen expression in B-chronic lymphocytic leukemia (B-CLL) is at significantly lower levels than in non-Hodgkins lymphoma, which may affect the degree of anti-CD20 antibody binding. Low density of CD20 expression on malignant cells may explain the lower response rates to anti-CD20 monoclonal antibody, observed in B-CLL. Upregulating the antigen receptor intensity on tumor cells may enhance the response rates. In this study, we examined the influence of granulocyte macrophage-colony stimulating factor (GM-CSF) on the expression level of CD20 antigen and percent of cells expressing CD20 antigen on B-CLL lymphocytes, in vivo. CD20 antigen expression was studied by flow cytometry at baseline, 12 and 24 h after GM-CSF injection. However neither upregulation of CD20 antigen nor a change of the proportion of CD20 positive cells was observed after a dose of 5 microg/kg GM-CSF. Strategies other than GM-CSF priming needs to be evaluated in order to increase the efficacy of anti-CD20 monoclonal antibodies in B-CLL.

Animals↗
PubMed1998

Clinico-prognostic relevance of quantitative immunophenotyping in B-cell chronic lymphocytic leukemia with emphasis on the expression of CD20 antigen and surface immunoglobulins.

Expression of CD20, evaluated as antibody binding capacity (ABC) (i.e. absolute number of molecules of antibody per cell), was analyzed using flow cytometry on leukemic cells of 93 previously untreated patients, all fulfilling strict criteria of "immunologically typical" (i.e. CD5+, CD23+) B-cell chronic lymphocytic leukemia (CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life-expectancy was observed in the low CD20 expression group compared with the high CD20 expression group (p = 0.05; relative risk of death, 0.51, 95% confidence interval, 0.24-1.04). Given the correlation between CD20 ABC and mean fluorescence intensity (MFI) of light chain (LC) surface immunoglobulins (Sm Ig) (r = 0.481, p < 0.0001), as well as the impact of MFI of Sm Ig LC on overall survival (p = 0.01; relative risk of death 0.44; 95% confidence interval, 0.10 to 0.76), we tried to verify whether a combination of B-cell markers, evaluated in a quantitative manner, could have additive prognostic properties. To this purpose we gave a value of 1 or 0 to each B-cell marker according to whether it was expressed at a low (i.e. CD20 ABC < 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig < 100) or high (i.e. CD20 ABC > or = 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig > or = 100) level thus allowing patient stratification into two groups with scores of 2 and 0-1, respectively. Survival of patients who scored 2 was significantly longer respectively. Survival of patients who scored 2 was significantly longer than that of patients who scored 0-1 (p = 0.02; relative risk of death, 0.44; 95% confidence interval, 0.22-0.72). However, when quantitative changes of CD20 antigen and LC Sm Ig expression, either alone or in combination, were simultaneously analyzed in a Cox model which included usual clinico-hematological features, only absolute peripheral blood lymphocytosis (p = 0.0001) and Binet clinical stages (p = 0.0001) maintained their prognostic power unmodified. Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B-cell CLL better, however, they cannot substitute well-established clinico-hematological features in the prognostic assessment of B-CLL patients.

Adult↗
PubMed2006

Pegylated interferon plus rituximab in advanced stage, indolent lymphoma: is there CD20 antigen upregulation?

The anti-CD20 monoclonal antibody, rituximab, and interferon alpha (IFN) are active agents in advanced stage, indolent lymphoma. Some data obtained in vitro suggest upregulation of CD20 by IFN, and clinical trials have reported additive or synergistic activity of IFN with rituximab. A prospective phase II study in advanced stage, follicular and non-follicular indolent lymphoma was performed. Peginterferon alpha 2b (pegIFN) 0.5 microg/kg s.c. weekly x 6 and rituximab 375 mg/m2 i.v. weekly x 4 (beginning on week 3 of pegIFN) was administered. Quantitative CD20 antigen was measured pre-treatment and pre-rituximab in lymph node aspirates. Nine patients were treated: one complete response and three partial responses; however, all relapsed within 12 months and two were withdrawn for grade 3 toxicity (both with serum sickness). No up-regulation of CD20 was documented in seven patients studied (median change in CD20: decrease by 11.9%). PegIFN plus rituximab as delivered in this study is not recommended. PegIFN does not appear to upregulate CD20 expression in peripheral lymph node tumor cells.

Aged↗
PubMed2000

Effect of interferon-alpha on CD20 antigen expression of B-cell chronic lymphocytic leukemia.

Chimeric CD20 monoclonal antibody as alternative therapy in relapsed low-grade non-Hodgkin's lymphoma (NHL) has produced responses in nearly 50% of patients. Augmenting CD20 expression on tumor cells and/or inducing its expression may increase the cell kill and effectiveness of antibody therapy. Peripheral blood lymphocytes from 19 patients with B-cell chronic lymphocytic leukemia (B-CLL) were incubated in vitro in the presence of interferon-alpha (IFN-alpha) (500 U/ml and 1,000 U/ml) for 24 and 72 hours. The effect on CD20 expression was studied by flow cytometry. The differences in the percentage positivity, the mean fluorescence intensity (MFI), and the product of percentage positivity and MFI were used to assess upregulation. There was a significant upregulation of CD20 expression on B cells seen at both concentrations after 24-hour priming (p < 0.01). B-CLL cells cultured for 72 hours in the presence of IFN-alpha also showed upregulation of CD20 expression; however, the degree of upregulation was much lower than that seen at 24 hours. There was no statistically significant increase in CD20 antigen expression on normal lymphocytes following cytokine exposure. These results suggest that IFN-alpha priming may augment the effectiveness of antibody therapy by directly upregulating CD20 antigen expression in addition to its indirect action through effector cells of the host.

Antigens, CD↗
PubMed1988

Cloning of a complementary DNA encoding a new mouse B lymphocyte differentiation antigen, homologous to the human B1 (CD20) antigen, and localization of the gene to chromosome 19.

The human B1 (CD20) molecule is a differentiation Ag found only on the surface of B lymphocytes. This structurally unique phosphoprotein plays a role in the regulation of human B cell proliferation and differentiation. In order to determine whether this structure is also expressed by murine B cells, cDNA clones that encode the mouse equivalent of the B1 molecule were isolated. The longest murine cDNA clone isolated, pmB1-1, contained a 1.4-kb insert with an 873 base pair open reading frame that encodes a protein of 32 kDa. The predicted mouse B1 protein contains three hydrophobic domains that may span the membrane four times and shares a 73% amino acid sequence homology with the human B1 protein. The pmB1-1 cDNA probe was used to examine mB1 mRNA expression. Northern blot analysis indicated that pmB1-1 hybridized with two mRNA species of 2.3 and 3.0 kb that were expressed only in murine spleen lymphocytes, in B lineage cell lines representing mature B cells, and were weakly expressed in one of two plasmacytoma cell lines. pmB1-1 failed to hybridize with RNA isolated from murine T cell lines, thymus, and nonlymphoid tissues. Southern blot analysis indicated that mB1 was encoded by a single copy gene. In situ hybridization localized the mB1 gene to chromosome 19 band B, a region that also contains the genes that encode the Ly-1, Ly-10, and Ly-12 Ag. These results suggest that only B cells express this heretofore undescribed murine cell-surface protein that is structurally homologous with the membrane-embedded human B1 Ag.

Amino Acid Sequence↗
PubMed2000

Effects of cytokines on CD20 antigen expression on tumor cells from patients with chronic lymphocytic leukemia.

Anti-CD20 antibody is an established treatment for low-grade non-Hodgkin's lymphoma (NHL). Augmenting the expression of CD20 antigen on the tumor cells may increase the cell kill and therefore increase the effectiveness of the antibody. To study this, we incubated peripheral blood lymphocytes from CLL patients with the following cytokines: EPO, SCF, TNFalpha, TGFbeta, GMCSF, TPO, IL-1, IL-2, IL-3, IL-4, GCSF. CD20 expression was studied by flow cytometry at baseline, 24 and 72 h after exposure to these cytokines. Upregulation of CD20 antigen expression was observed with IL-4, TNFalpha and GMCSF.

Antigens, CD20↗
PubMed1996

Transient expression of CD20 antigen (pan B cell marker) in activated lymph node T cells.

In contrast to the case of peripheral T cells, the surface expression of CD20 antigen and the expression of CD20 mRNA in monkey lymph node (LN) T cells underwent a noticeable increase when they were cultured with mitogen and interleukin-2 (IL-2). To confirm in vivo regulation of CD20 expression during the activation of LN T cells, we examined LNs derived from monkeys experimentally inoculated with simian immunodeficiency virus (SIV). Significant expression of CD20 antigen was detected in the T cells of the LNs at the stage of lymphadenopathy. These findings suggest that lymphocyte activation in the LNs induced expression of the CD20 molecule in some T cells.

Animals↗
PubMed2006

[Density expression of the CD20 antigen on population of tumor cells in patients with chronic B-lymphocyte lymphoproliferative diseases].

BACKGROUND: Rituximab is being used successfully in the treatment of patients with chronic B-cell lymphoproliferative diseases. The success of treatment by rituximab is influenced, among other factors, by the antigen density on tumor cells. Therefore, the authors analyzed and compared the densities of the CD20 antigen in patients with chronic lymphoproliferative diseases. METHODS AND RESULTS: Previously untreated patients with B-chronic lymphocytic leukemia (B-CLL), mantle-cell lymphoma (MCL), and small-cell lymphocytic lymphoma (SCLL) were evaluated by flow cytometry. The control group consisted of blood donors. The CD20 density was measured on tumor cell populations in patients and on the B-lymphocytes of the control group. The density was expressed in MESE In the patients with B-CLL and SCLL, the CD20 density was low (25,300 vs. 36,100 MESF) and it was significantly lower than in donors (172,800 MESF; p<0.001). The difference between B-CLL and SCLL patients was not statistically significant. The density in MCL patients (196,300 MESF) was comparable to that of donors. CONCLUSIONS: We did not prove statistical different density of CD20 antigen in patients with SCLL when compared with B-CLL patients. High density in MCL patients may be helpful in differential diagnosis against B-CLL and

Aged↗
PubMed1999

Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression.

Rituximab is a chimeric antibody with human gamma-1 and kappa constant regions and murine variable regions. It recognizes the CD20 antigen, a pan B-cell marker. Therapeutic trials in patients with B-cell non-Hodgkin's lymphoma (NHL) have shown significant efficacy with a primary response rate of 50%, and a secondary response rate of 44% after repeat treatments in prior responders. The selection for proliferating tumor cells that no longer express CD20 may compromise repeated treatment. We have identified a patient who developed a transformed NHL that lost CD20 protein expression after two courses of therapy with rituximab. In a pretreatment lymph node biopsy, 83% of B cells (as defined by CD19 and surface immunoglobulin) expressed surface CD20. A biopsy from the recurrent tumor after two courses of rituximab revealed a diffuse large cell NHL where 0% of B cells expressed CD20 with no evidence of bound rituximab. Cytoplasmic staining showed no CD20 protein. Sequencing of immunoglobulin heavy chain cDNA identified identical variable sequences in the initial and recurrent lymphomas, confirming the association between the two tumors. Literature and database review suggests that approximately 98% of diffuse large cell lymphomas express CD20, which suggests that these tumors rarely survive without CD20. This is the first identified case of loss of CD20 expression in a lymphoma that has relapsed after rituximab therapy, although several other cases have since been identified. Considering the significant number of patients treated with anti-CD20 antibodies, this may occur only rarely and is unlikely to preclude recurrent therapy with anti-CD20 antibodies in the majority of patients. However, because many patients have relapsed after anti-CD20 antibody therapy and have not been biopsied to identify clones with down-regulated CD20 antigen, we do not currently know the true frequency of this phenomenon. When possible, patients should undergo evaluation for CD20 expression before repeated courses of anti-CD20 therapy.

Antibodies, Monoclonal↗
PubMed1990

Antibody L26 recognizes an intracellular epitope on the B-cell-associated CD20 antigen.

Monoclonal antibody L26 is a highly selective marker of B cells and B-cell neoplasms in paraffin-embedded tissues, but it suffers from the drawback that the target molecule has not been identified. In this paper we provide evidence by two independent techniques that antibody L26 recognizes an intracellular epitope on the CD20 antigen (a pan B-cell marker). When this antigen was redistributed on the surface of unfixed viable B cells by incubation with monoclonal anti-CD20 followed by anti-mouse Ig, the diffuse cytoplasmic staining of L26 was abolished and replaced by coincident dotlike labeling for antibody L26 and the CD20 antigen. None of the other antibodies tested (covering 10 different B-cell-associated antigens) had this effect on the L26 staining pattern. Furthermore, COS-1 cells transfected with cDNA encoding the CD20 molecule gave positive staining with antibody L26 and with two other CD20 reagents, but not with antibodies to other pan B-cell markers (eg, CD19 and CD22).

Antibodies, Monoclonal↗
PubMed1994

Detection of trisomy 12 by FISH in untreated B-chronic lymphocytic leukemia: correlation with stage and CD20 antigen expression intensity.

We studied cells from 30 controls and 85 cases of untreated B-chronic lymphocytic leukemia (CLL) with a fluorescence in-situ hybridization (FISH) technique utilizing a probe to chromosome 12. By use of a threshold of > 2% for trisomy 12 for the CLL cases (the mean +3 SD for controls was 1.3%), 20% (17/85) were trisomy 12. The mean % cells positive was 32.6 (median, 39.4; range, 2.4-79.1). There was a trend toward an higher incidence of trisomy 12 in patients with Rai stages 1-4 vs Rai 0 (p = 0.16). Forty-seven % (8/17) of patients with trisomy 12 had strong intensity CD20 antigen expression compared to 21% (14/68) of patients without trisomy 12 (p = 0.03). Trisomy 12 associated with CLL is easily detected by FISH with an overall incidence of 20%. This technique should be applied to larger groups of patients to confirm the potential variation among Rai stages and immunophenotypic subgroups.

Antigens, CD↗
PubMed1993

Interleukin-7 enhances colony growth and induces CD20 antigen of a Ph+ acute lymphoblastic leukemia cell line, OM9;22.

A newly established human leukemia cell line, OM9;22, is reported, with B-precursor immunophenotype (CD10+ CD19+ CD22+ HLA- DR+ C mu-) and CD13 antigen, originated from a 19-year-old female patient with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL). The OM9;22 cells carry a Philadelphia (Ph) translocation and hybrid message detected by a minor-breakpoint cluster region (BCR) exon 1/ABL exon 2 junctional probe using reverse transcriptase polymerase chain reaction. The genetic alterations are consistent with those observed in the donor's leukemia cells, allowing us to conclude that this cell line is a minor-BCR rearranged Ph-positive ALL (Ph+ ALL). Colony formation of the OM9;22 cells in methylcellulose culture is enhanced by the addition of human interleukin 7 (IL-7). In liquid culture, more than 80% of IL-7-treated OM9;22 cells express CD20 antigen but fail to express surface immunoglobulins or cytoplasmic mu-chain, indicating that the cells have a potential of limited maturation by IL-7. By contrast, IL-4 suppresses the colony formation of the OM9;22 cells. These findings suggest that this cell line might be a model of B-precursor human leukemia with proliferative capability by IL-7.

Adult↗
PubMed2003

An oncolytic measles virus engineered to enter cells through the CD20 antigen.

We have earlier shown that attenuated measles virus (MV) has therapeutic potential as a replicating oncolytic virus in models of non-Hodgkin's lymphoma (NHL). In the current study, we investigated whether we could obtain replicating MVs capable of entering CD20(+) target cells through an interaction between a single-chain (scFv) anti-CD20 antibody and the CD20 antigen, a target of considerable clinical relevance in NHL. We replaced the H envelope glycoprotein of MV by an H-scFv anti-CD20 fusion protein with and without a protease-cleavable linker. Biochemical analysis of purified virions confirmed that the modified H proteins were incorporated into the viral particles with efficiency similar to unmodified H. Experiments employing CHO cells and CHO cells expressing human CD20 indicated that the MVH alpha CD20 viruses were able to replicate well in CHOCD20 but not CHO cells. MVH alpha CD20 or a nonmodified control MV were administered systemically to immunodeficient mice bearing bilateral human tumor xenografts, one side with and the other side without CD20 expression. Growth of CD20(+) tumors was retarded by MVH alpha CD20 as compared with the control virus. The viruses had equivalent effects on the CD20(-) tumors. Thus we have demonstrated that the entry of a replicating oncolytic virus can be mediated through an interaction between a highly clinically relevant single-chain antibody and its target antigen, and we have shown that this interaction enhances in vivo oncolytic activity.

Amino Acid Sequence↗
PubMed2003

Refractory autoimmune thrombocytopenic purpura: responses to treatment with a recombinant antibody to lymphocyte membrane antigen CD20 (rituximab).

"Refractory" autoimmune thrombocytopenia represents a life-threatening condition, having failed to respond to a variety of therapeutic measures. We report a series of cases, all failing splenectomy and multiple therapeutic programs, including, in two patients, marrow transplant. Five of the six cases reported responded to a recombinant antibody to the lymphocyte membrane antigen CD20 (rituximab), an agent commonly employed in the treatment of non-Hodgkin's lymphoma. Our experiences over a period of 4 years are documented. The results support the use of this product, rituximab, in the treatment of patients with autoimmune thrombocytopenia who have not attained a hemostatically effective platelet count following splenectomy and require a continuing therapeutic management program.

Adult↗
PubMed1989

Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1).

The CD20 (B1) molecule is a differentiation Ag found only on the surface of B lymphocytes. This structurally unique phosphoprotein plays a role in the regulation of human B cell proliferation and differentiation. In this report genomic DNA clones containing the human CD20 gene were isolated and the structure of the CD20 gene determined. Southern blot analysis revealed that CD20 mRNA was transcribed from a single-copy gene. The CD20 gene was 16 kb long and was composed of eight exons. The first exon marked the major transcription initiation site as determined by primer extension and S1 nuclease analysis. The translation initiation codon was located within the third exon. Exon VIII encoded the COOH terminus of the CD20 protein and the long 3' untranslated region. Three forms of CD20 mRNA were identified that all encode an identical protein product. The dominant form of 2.8 kb results from usage of exons I through VIII, whereas a second form that is 263 bp shorter had exon I spliced into an internal 3' splice site within exon III thereby skipping exon II. A minor 3.4-kb mRNA species most likely results from an uncharacterized upstream exon(s) splicing into an internal 3' slice site located in exon I. Nucleotide sequences of cDNA clones representative of each of these RNA forms are presented. The 5' splice site following exon V was found to be divergent from the consensus splice sequence. A relationship between the individual peptides encoded by the six exons and structurally distinct regions of the CD20 protein is likely.

Amino Acid Sequence↗