Control of human B cell tumor growth in severe combined immunodeficiency mice by monoclonal anti-B cell antibodies.

Severe combined immunodeficiency (scid) mice develop EBV (+)B cell tumors after infusion of EBV(+)B cells or of B cells and EBV. In this study, scid mice were infused with B cell lines derived from three patients who developed a B lymphocyte proliferative disorder after bone marrow or organ transplantation. Intraperitoneal injection of 5 x 10(6) B cells induced tumor growth in all mice, leading to death within 60 d. Human B cells were identified in spleen and bone marrow by means of immunofluorescence or EBV genome amplification, and human IgM was detected in serum. Infusion of murine monoclonal antibodies specific for human B cell membrane antigens CD21, CD24, and CD23 was effective in 80% of animals, against two of the three cell lines preventing tumor development or inducing remission according to the time of treatment. The effect was antibody dose dependent and was optimal with four intravenous infusions of at least 0.1 mg 4 d apart. Human IgM in serum and human B cells in spleen and bone marrow became undetectable when peritoneal tumors regressed completely. Infusions of IgG1 isotype-matched anti-CD4 antibody or anti-CD3 antibody had no effect. Tumors developed or recurred in 50% of these animals injected with one of the B cell line 3 mo after treatment was stopped. The same anti-CD21 and anti-CD24 antibodies had been used to treat the three patients, and shown similar degrees of effectiveness as in the scid mouse model. These results indicate that scid mice may be suitable for assessing therapeutic approaches to human B cell proliferation.     

338例 EB病毒五项抗体与白细胞检测结果的研究分析

目的： EB病毒五项抗体与白细胞检测结果的相互关系。方法使用酶联免疫吸附试验（ELISA ）检测EB病毒五项抗体、阻抗法检测白细胞计数和分类,回顾性分析338例EB病毒五项抗体与白细胞检测的结果,采用SPSS11．5对检验数据进行χ2检验、t检验进行分析。结果 EB病毒抗体五项结果全部“阴性”的、EB病毒抗原（VCA）‐IgG抗体、EB病毒核抗原（EBNA1） IgG抗体二者“阳性”的;EB病毒抗原（VCA）‐IgG抗体、EB病毒早期抗原（EA）IgG抗体、EB病毒核抗原（EBNA1）IgG抗体三者“阳性”的白细胞计数和分类结果均在各自生物参考区间范围之内;EB病毒抗原（VCA ）‐IgA抗体、EB病毒抗原（VCA ）IgM 抗体、EB病毒早期抗原（EA）IgG抗体、EB病毒核抗原（EBNA1）IgG抗体四者“阳性”的白细胞计数和分类均在各自生物参考区间范围下限;EB病毒抗原（VCA ）IgM抗体“阳性”的白细胞计数低于生物参考区间范围下限。白细胞分类中淋巴细胞分类结果增高,中性粒细胞分类结果在生物参考区间上限,其余三类结果正常。结论 EB病毒五项抗体与白细胞检测结果有一定的相关性,有助于EB V感染的早期诊断,联合检测两类指标可提高EB V现症感染的检出率。     

Epstein-Barr virus nuclear antigens 1 and 2 in Burkitt lymphoma cell lines containing either 'A'- or 'B'-type virus

Epstein-Barr virus (EBV) has previously been classified into two different types according to the organization of the EB nuclear antigen 2 (EBNA2) gene region. Type A virus hybridizes with probes from B95-8 or M-ABA viruses and the B type virus with probes from the Jijoye virus strain. The substituted region in EBV type B codes for a different, but related EBNA2 antigen, named EBNA2B as opposed to EBNA2A. In this study Burkitt lymphoma cell lines, previously typed according to the EBV viral genomes they carry, as well as some matching lymphoblastoid cell lines were examined by immunoblotting for the expression of both EBNA1 and EBNA2 antigens. Variation in the molecular weight of EBNA1 indicated that both A and B virus types contained a variety of different virus isolates. EBNA2A was identified in all lines carrying A type viral genomes, but was not observed in any of the lines harboring B type virus. EBNA2B was identified in 4 of 10 Burkitt lymphoma lines carrying EBV type B.     

Transforming activity and antigenicity of an Epstein-Barr-like virus from lymphoblastoid cell lines of baboons with lymphoid disease.

Two lymphoblastoid cell lines were established from baboons with lymphoid disease. Cells of these lines were positive for complement and Fc receptors but lacked sheep cell receptors, theraby indicating B-cell origin. The cells contained antigens which cross-reacted with Epstein-Barr virus (EBV), viral capsid antigen (VCA), early antigen (EA) and membrane antigen (MA). Both lines released virus with in vitro transforming activity for lymphocytes of several primate species including humans. Cells of the original lines and transformed cells showed no staining for EB nuclear antigen (EBNA). The virus was neutralized by anti-MA positive baboon and human sera. Baboon virus and EBV had different but overlapping in vitro host-cell ranges.     

EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors

Epstein-Barr virus (EBV) persistently infects more than 90% of the human population and is etiologically linked to several B cell malignancies, including Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and diffuse large B cell lymphoma (DLBCL). Despite its growth transforming properties, most immune-competent individuals control EBV infection throughout their lives. EBV encodes various oncogenes, and of the 6 latency-associated EBV-encoded nuclear antigens, only EBNA3B is completely dispensable for B cell transformation in vitro. Here, we report that infection with EBV lacking EBNA3B leads to aggressive, immune-evading monomorphic DLBCL-like tumors in NOD/SCID/γc-/- mice with reconstituted human immune system components. Infection with EBNA3B-knockout EBV (EBNA3BKO) induced expansion of EBV-specific T cells that failed to infiltrate the tumors. EBNA3BKO-infected B cells expanded more rapidly and secreted less T cell-chemoattractant CXCL10, reducing T cell recruitment in vitro and T cell-mediated killing in vivo. B cell lines from 2 EBV-positive human lymphomas encoding truncated EBNA3B exhibited gene expression profiles and phenotypic characteristics similar to those of tumor-derived lines from the humanized mice, including reduced CXCL10 secretion. Screening EBV-positive DLBCL, HL, and BL human samples identified additional EBNA3B mutations. Thus, EBNA3B is a virus-encoded tumor suppressor whose inactivation promotes immune evasion and virus-driven lymphomagenesis.     

Oligonucleotides for polymerase chain reaction amplification and hybridization detection of Epstein-Barr virus DNA in clinical specimens

We designed synthetic oligonucleotide primers and hybridization probe for use in polymerase chain reaction (PCR) amplification and hybridization detection of Epstein-Barr virus (EBV) nucleic acid sequences. Primer sequences were chosen from the coding region for the Epstein-Barr virus nuclear antigen-1 (EBNA-1). PCR amplification and hybridization with these oligonucleotides was carried out on standard laboratory cell lines including African Burkitt's lymphoma and infectious mononucleosis derived cell lines, as well as cell lines recently established from clinical EBV isolates from bone marrow transplant recipients. All EBV cell lines tested were positive. No false-positives were detected with uninfected cell lines, human placental DNA or with other viruses. The sensitivity of the detection procedure was such that four copies of the EBV genome could consistently be detected in a background of 1 microgram of placental DNA. EBV was detected in DNA extracts from the peripheral blood mononuclear cells of two patients with infectious mononucleosis and one patient with viral-associated hemophagocytic syndrome. Three of 18 EBV seropositive patients without known ongoing EBV-associated illness undergoing ambulatory surgery also had EBV detected in DNA extracts from their peripheral blood mononuclear cells. EBV was detected in DNA extracts from lymphoma tissue from two patients with post-transplant lymphomas and two AIDS patients with primary CNS lymphomas. EBV was not detected in 12 B-cell lymphoma specimens from patients without history of immunocompromise. DNA extracts from formalin-fixed paraffin-embedded Hodgkin's tissues previously shown to be EBV positive by Southern blot were also demonstrated to be EBV positive by PCR. Thus, with the oligonucleotides described, PCR is applicable to the detection of EBV in a spectrum of clinical isolates. The broad specificity of these oligonucleotides for all strains of EBV tested is probably a function of the highly conserved sequence of the EBNA-1 DNA binding domain.     

Complementation between infecting Epstein-Barr virus and intrinsic viral genomes in human lymphoid cell lines

13 human lymphoid cell lines previously characterized in terms of their intrinsic Epstein-Barr virus (EBV) genome content were infected or superinfected with EBV from the supernatant of P3HR-1 cells. The cell lines included 2 lymphoma cell lines that contain no detectable EBV genomes and 11 cell lines containing intrinsic EBV genomes. All the cell lines responded to EBV infection by expressing early antigen (EA). The number of EA-positive cells in the cultures was proportional to the viral concentration used for infection or superinfection. However, cell lines containing multiple intrinsic EBV genomes expressed higher amounts of EA-positive cells. Evaluation of EA expression versus the number of intrinsic EBV genome copies per cell in each line revealed EA to increase as the intrinsic EBV genome content of the cell lines increased in a nonlinear curve that was described by an exponential logistic function. The coefficient of determination R2 for this curve was greater than 0.9 for multiple experiments. The data suggest that 80-90% of the virus in P3HR-1 is defective and requires intrinsic viral genomes for expression of EA. Transactivation or complementation between intrinsic EBV genomes and infecting virus is supported by these observations.     

人类免疫缺陷病毒感染相关淋巴瘤的临床病理学观察

目的探讨人类免疫缺陷病毒(HIV)感染相关淋巴瘤的临床病理学特点、与EB病毒感染的关系。方法对3例HIV感染相关淋巴瘤的标本进行病理形态学、免疫组化及EB病毒原位杂交观察。结果 3例中2例诊断为伯基特淋巴瘤,1例诊断为弥漫性大B细胞淋巴瘤。免疫组化3例均表达B细胞标记物(CD20),Ki-67指数均较高。3例EB病毒原位杂交均阳性。结论 HIV感染相关淋巴瘤发生的类型主要是高度恶性B细胞淋巴瘤,与EB病毒感染关系密切。     

NK细胞淋巴瘤的分类及其病理诊断

近年自然杀伤细胞(NK细胞)肿瘤的研究与诊断有很大进展。新的NK细胞分类将其分为EB病毒相关与EB病毒不相关两大类。前者包括鼻和鼻型NK细胞淋巴瘤、侵袭性NK细胞白血病,后者包括皮肤原发的母细胞性NK细胞淋巴瘤和NK细胞淋巴母细胞性淋巴瘤。本文对各种NK细胞淋巴瘤/白血病的鉴别诊断和免疫表型、EB病毒潜伏感染检测的作用进行评估。     

Epstein-Barr virus: the spectrum of its manifestations in human beings

Epstein-Barr virus (EBV) infects virtually everyone by adulthood, and a lifelong latency is maintained. It infects children silently, whereas the majority of adolescents have infectious mononucleosis (IM). Children who have IM before 5 years of age are often heterophil negative; EBV-specific antibodies are required for diagnosis. On rare occasions the symptoms of IM may persist in a chronic or recurrent form, and fatal infectious mononucleosis occurs rarely. Depending on the type and degree of immune deficiency and the time the EBV infection occurs in the life cycle, various atypical outcomes can occur. Children with primary immune deficiency can have fatal or chronic IM, malignant B cell lymphoma, virus-associated hemophagocytic syndrome, aplastic anemia, or acquired hypogammaglobulinemia. The various outcomes of the EBV infections are likely governed by the immune response of the individual. The increased frequency of B cell neoplasms in immunodeficient patients is likely due, in part, to EBV. Individuals with acquired immune deficiency disorders such as AIDS or allograft recipients may develop malignant B cell lymphomas which tend to be polyclonal, but which may progress through stages of oligoclonality to monoclonality. This conversion likely results from specific reciprocal chromosomal translocations such as t(8;14), which is seen in Burkitt's lymphoma. Detection of EBV in immunodeficient patients is achieved by EBV-specific antibody studies or isolation of virus by obtaining spontaneous lymphoblastoid cell lines from peripheral blood, isolating virus from throat washings, or identifying EBV genome by molecular hybridization techniques. Prevention of primary immune deficiency by early detection and genetic counseling and monitoring of patients for occurrence of EBV infection may lead to early treatment. Acyclovir and immunoglobulin therapy can be of value in some patients with active EBV infection.     

Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man

When human peripheral blood lymphocytes (PBLs) from Epstein-Barr virus (EBV)-seropositive donors are injected intraperitoneally into SCID mice, EBV+ B cell tumors develop within weeks. A preliminary report (Mosier, D. E., R. J. Gulizia, S. M. Baird, D. D. Richman, D. B. Wilson, R. I. Fox, and T. J. Kipps, 1989. Blood. 74(Suppl. 1):52a) has suggested that such tumors resemble the EBV-positive malignancy, Burkitt's lymphoma. The present work shows that generally the human (hu) PBL-SCID tumors are distinct from Burkitt's lymphoma and instead resemble lymphoblastoid cell lines (LCLs) generated by EBV-infection of normal B cells in vitro in terms of: (a) their cell surface phenotype, with expression of B cell activation antigens and adhesion molecules, (b) normal karyotype, and (c) viral phenotype, with expression of all the transformation-associated EBV latent proteins and, in a minority of cells, productive cycle antigens. Indeed, in vitro-transformed LCLs also grow when inoculated into SCID mice, the frequency of tumor outgrowth correlating with the in vitro growth phenotype of the LCL which is itself determined by the identity of the transforming virus (i.e., type 1 or type 2 EBV). Histologically the PBL-derived hu-SCID tumors resemble the EBV+ large cell lymphomas that develop in immuno-suppressed patients and, like the human tumors, often present at multiple sites as individual monoclonal or oligoclonal foci. The remarkable efficiency of tumor development in the hu-SCID model suggests that lymphomagenesis involves direct outgrowth of EBV-transformed B cells without requirement for secondary genetic changes, and that selection on the basis of cell growth rate alone is sufficient to explain the monoclonal/oligoclonal nature of tumor foci. EBV+ large cell lymphoma of the immunosuppressed may arise in a similar way.     

An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection.

An in vitro line was derived from an American Burkitt lymphoma, designated Ra No. 1, which produced malignant tumors when inoculated into thymus-deficient nude mice. The cells have B-lymphocyte characteristics, with surface-associated mu and kappa chains and Epstein-Barr virus (EBV) receptors, and can be readily infected with EBV in vitro. B95-8 virus induced EBV-determined nuclear antigen (EBNA) but not early antigen (EA) in Ra No. 1 cells, whereas P3HR-1 virus induced both EBNA and EA, but the EA level was much lower than in the prototype Raji strain, EBNA and EA levels were comparable in Ra No. 1 and in the previously established, EBV-infection-sensitive BJA-B lymphoma. The two lines differed, however, because BJA-B could be converted into a permanent EBV-carrying line by the B95-8 but not by the P3HR-1 virus strain, whereas Ra No. 1 could be converted by the P3HR-1 virus. This demonstrates that different B-lymphocyte-derived lymphoma lines can vary with regard to the restrictive control they can exert on the same virus strain. Furthermore, virus strains vary in their sensitivity to the restrictions of the same host cell. Permanent EBV conversion of the Ra No. 1 cell did not appear to change the cellular controls, as judged by the unchanged sensitivity of the cell to viral antigen (EA, viral capsid antigen) induction by P3HR-1 virus superinfection.     

淋巴系统肿瘤发病与EB病毒和IL-10基因多态性的关系

淋巴系统肿瘤与病毒感染有密切关系,EBV(Epstein-Barn Virus)转染正常B细胞会造成B细胞发生类似肿瘤的永生化,是最可疑的致病因素.EBV的Bcrfl编码框又称为病毒IL-10,和人类IL-10同源,具有和IL-10相似的免疫抑制作用.IL-10是一种重要的免疫调节因子,其分泌水平的高低影响着淋巴系统疾病的发生和发展;IL-10启动子区的SNP位点基因型也与IL-10的分泌水平相关.本综述探讨淋巴系统肿瘤,EBV感染以及IL-10基因多态性之间的密切关系.     

The role of Epstein-Barr virus in cancer

Epstein-Barr virus (EBV), discovered > 40 years ago from a Burkitt's lymphoma biopsy, was the first virus to be directly associated with human cancer. EBV has two distinct life cycles in the human host; a lytic form of infection that produces new infectious virions, and a latent form of infection that allows the virus to persist in a dormant state for the lifetime of the host. EBV has evolved a life cycle that mimics the natural differentiation pathway of antigen-activated B cells, giving the virus access to its site of latent infection, the resting memory B cell. By steering infected cells through the various stages of lymphocyte differentiation, EBV is able to enter a cell type suitable for long-term latent persistence and periodic reactivation. However, its presence in various stages of B-cell development, and its ability to infect certain epithelial cells, can have pathogenic consequences, and can contribute to the development of a diverse group of lymphomas and carcinomas. The presence of EBV in the tumour cells of EBV-associated cancers might provide a basis for specific therapy. This article focuses on the contributions that the virus may play in different types of human cancer, particularly Burkitt's lymphoma, Hodgkin's lymphoma, lymphomas and lymphoproliferative diseases in the immunocompromised, and nasopharyngeal and gastric carcinoma.     

RON基因在淋巴瘤的表达及与EB病毒感染相关性研究

目的 研究RON基因在不同淋巴瘤组织及其细胞株中的表达情况及与EB病毒感染的相关性. 方法 通过免疫组织化学染色法检测淋巴瘤患者以及正常和炎性淋巴组织RON的表达,计算RON阳性组织的比例及RON蛋白表达阳性标记强度特征;蛋白免疫印迹法检测淋巴瘤细胞株RON的表达情况;并且用原位杂交的方法检测EBV编码的小RNA （EBER）在伯基特淋巴瘤和霍奇金淋巴瘤组织的表达情况.结果 RON在霍奇金淋巴瘤和伯基特淋巴瘤组织中阳性率分别为55.0％ （11/20）、66.7％（8/12）,高于其在良性淋巴组织（正常淋巴组织及炎性淋巴组织）中的表达（P均＜0.05）.进一步发现霍奇金淋巴瘤和伯基特淋巴瘤组织芯片及其细胞株L428和Raji细胞株中RON表达水平远高于其他淋巴瘤.霍奇金淋巴瘤和伯基特淋巴瘤中EB病毒的阳性和RON过表达相关性密切.结论 RON在淋巴瘤中表达呈异质性,其中伯基特淋巴瘤和霍奇金淋巴瘤中高表达,而且两者的RON过表达和EB病毒感染密切相关.     

Human Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes home preferentially to and induce selective regressions of autologous EBV- induced B cell lymphoproliferations in xenografted C.B-17 scid/scid mice [published erratum appears in J Exp Med 1996 Sep 1;184(3):1199]

C.B-17 scid/scid (severe combined immunodeficiency [SCID]) mice inoculated with peripheral blood lymphocytes from Epstein-Barr virus (EBV)-seropositive donors, or with EBV-transformed lymphoblastoid B cell lines (EBV-LCL), develop lethal human EBV+ B cell lymphoproliferative disorders (EBV-LPD) with characteristics similar to those arising in immunodeficient patients. Using this model, we examined the capacity of human effector cells to control human EBV-LPD. SCID mice received rabbit anti-asialo GM1 antiserum to abrogate endogenous natural killer-cell function. Preliminary experiments showed that adoptive transfer of peripheral blood mononuclear cells (PBMC), purified T cells, interleukin (IL) 2-activated PBMC or anti-CD3- activated T cells derived from EBV-seropositive donors did not result in improved survival of treated mice (in vivo effector/target ratio 2:1 to 1:1). In contrast, EBV-specific cytotoxic T lymphocytes (CTL), derived from EBV-seropositive donors and expanded in vitro, exhibited strong EBV-specific and HLA-restricted activity both in vitro and in vivo. SCID mice inoculated intraperitoneally with autologous but not with HLA-mismatched EBV-LCL had significantly improved survival relative to untreated mice after inoculation of EBV-specific CTL either intraperitoneally (P<0.001) or intravenously (P<0.001) (in vivo effector/target ratio 1:1). SCID mice bearing large subcutaneous EBV+ tumors and treated intravenously with 10(7) EBV-specific CTL achieved complete tumor regression. Both CTL- and CTL-plus-IL-2-treated mice survived significantly longer than untreated animals or animals treated with IL-2 alone (P = 0.0004 and P<0.02, respectively). SCID mice bearing two subcutaneous EBV+ tumors, one autologous and the other HLA mismatched to the EBV-specific CTL donor, had regression of only the autologous tumor after intravenous infusion of 10(7) EBV-specific CTL. Moreover, we could demonstrate preferential homing of PKH26-labeled EBV- specific CTL to autologous but not to HLA-mismatched EBV+ tumors as early as 24 h after intravenous adoptive transfer. Immunophenotypic analyses also demonstrated preferential infiltration of T cells into the autologous EBV+ tumor in SCID mice bearing both the autologous and either fully HLA-mismatched or genotypically related haplotype-sharing EBV+ tumors. The human T cells infiltrating EBV+ tumors were CD3+ and, predominantly, CD8+CD4-. Our results indicate that EBV-specific CTL preferentially localize to and infiltrate EBV+ tumors bearing the appropriate HLA antigens and thereafter induce targeted regressions of disease.     

The role of Epstein–Barr virus in cancer

Epstein–Barr virus (EBV), discovered > 40 years ago from a Burkitt’s lymphoma biopsy, was the first virus to be directly associated with human cancer. EBV has two distinct life cycles in the human host; a lytic form of infection that produces new infectious virions, and a latent form of infection that allows the virus to persist in a dormant state for the lifetime of the host. EBV has evolved a life cycle that mimics the natural differentiation pathway of antigen-activated B cells, giving the virus access to its site of latent infection, the resting memory B cell. By steering infected cells through the various stages of lymphocyte differentiation, EBV is able to enter a cell type suitable for long-term latent persistence and periodic reactivation. However, its presence in various stages of B-cell development, and its ability to infect certain epithelial cells, can have pathogenic consequences, and can contribute to the development of a diverse group of lymphomas and carcinomas. The presence of EBV in the tumour cells of EBV-associated cancers might provide a basis for specific therapy. This article focuses on the contributions that the virus may play in different types of human cancer, particularly Burkitt’s lymphoma, Hodgkin’s lymphoma, lymphomas and lymphoproliferative diseases in the immunocompromised, and nasopharyngeal and gastric carcinoma.     

The molecular biology of Epstein-Barr virus

Epstein-Barr virus (EBV) was discovered in continuously growing tumor cells derived from African patients with Burkitt's lymphoma. In the intervening twenty years, much biological and biochemical information has been accumulated. The virus infects B lymphocytes and occupies a unique position among human herpesviruses in that it is the only one which is capable of forming a latent infection whereby complete copies of the virus genome persist in growth transformed cells. Since there are no fully permissive cell systems of virus replications, only the established B cell lines are available for study of the molecular events of EB virus in infected cells. A viral cycle consists of four stages, latent, early replicative, middle replicative and late replicative stages. In the latent state, only small parts of the viral genome are transcribed and express transformation proteins: nuclear antigens (EBNAs) and lymphocyte determined membrane antigen (LYDMA). After reactivation of viral genome and during a productive cycle, more than 50 RNAs are expressed and over 30 viral-specified polypeptides are detectable by immunoprecipitation with a high titer human anti-EBV serum. During the early replicative stage, early antigens (EA) and DNA enzymes, both necessary for DNA synthesis, are synthesized. In the late replicative stage, about 30-40 mRNA are transcribed and two major late antigen complexes, viral capsid antigens (VCA) and membrane antigens (MA), are identified. These antigens are indispensable for the formation of virions.     

EB病毒与其相关淋巴瘤的研究进展

EB病毒（Epstein-Barr virus,EBV）属于r-DNA疱疹病毒科,是最早被发现与人类肿瘤相关的病毒。大量研究发现,EBV的感染与多种淋巴瘤的发生有关,如霍奇金淋巴瘤、伯基特淋巴瘤、NK/T细胞淋巴瘤、HIV相关的淋巴瘤和弥漫大B细胞淋巴瘤等。近年来研究表明,EBV潜伏感染的基因表达产物对淋巴瘤的发生发展起到促进作用,并为EBV相关淋巴瘤的治疗提供了依据。现就EBV在几种常见淋巴瘤中的作用机制及治疗的研究进展做如下综述。     

Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10

Interleukin 10 (IL-10) is a pleiotropic factor that enhances proliferation of activated human B lymphocytes and induces them to secrete high amounts of immunoglobulins. Here we show that several human B cell lines were able to constitutively secrete human (h)IL-10. Whereas none of the pre-B nor the plasmocytic cell lines tested produced hIL-10, 25 of the 36 tested mature B cell lines (lymphoblastoid and Burkitt lymphoma cell lines) secreted hIL-10. Moreover, 24 of these 25 hIL-10-producing B cell lines contained the Epstein-Barr virus (EBV) genome, suggesting a relationship between hIL- 10 production by human B cell lines and EBV expression. Accordingly, whereas polyclonal activation via triggering of surface immunoglobulins or CD40 antigen induced highly purified normal human B lymphocytes to produce only low (0.3-0.4 ng/ml) but significant amounts of hIL-10, EBV infection induced them to secrete high amounts of hIL-10 (4-9 ng/ml). Furthermore, addition of exogenous hIL-10, simultaneously to EBV infection, potentiated cell proliferation, whereas a blocking anti-IL- 10 antiserum inhibited it. Thus, hIL-10 produced by infected human B lymphocytes appears to be involved in the mechanisms of EBV-induced B cell proliferation.