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It is well established that B cells play an important role during infections beyond antibody production. B cells produce cytokines and are APCs for T cells. Recently, it has become clear that several pathogenic bacterial genera, such as Salmonella, Brucella, Mycobacterium, Listeria, Francisella, Moraxella, and Helicobacter, have evolved mechanisms such as micropinocytosis induction, inflammasome down-regulation, inhibitory molecule expression, apoptosis induction, and anti-inflammatory cytokine secretion to manipulate B cell functions influencing immune responses. In this review, we summarize our current understanding of B cells as targets of bacterial infection and the mechanisms by which B cells become a niche for bacterial survival and replication away from extracellular immune responses such as complement and antibodies., (©2019 Society for Leukocyte Biology.)

Lipophilic copper (Cu)-containing complexes have shown promising antibacterial activity against a range of bacterial pathogens. To examine the susceptibility of the intracellular human pathogen Chlamydia trachomatis to copper complexes containing bis(thiosemicarbazone) ligands [Cu(btsc)], we tested the in vitro effect of CuII-diacetyl- and CuII-glyoxal-bis[N(4)-methylthiosemicarbazonato] (Cu(atsm) and Cu(gtsm), respectively) on C. trachomatis. Cu(atsm) and to a greater extent, Cu(gtsm), prevented the formation of infectious chlamydial progeny. Impacts on host cell viability and respiration were also observed in addition to the Chlamydia impacts. This work suggests that copper-based complexes may represent a new lead approach for future development of new therapeutics against chlamydial infections, although host cell impacts need to be fully explored., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides., (© 2015 British Society for Immunology.)

Regulated production of ROS is mainly attributed to Nox family enzymes. In neutrophil granulocytes and macrophages, Nox2 has a crucial role in bacterial killing, and the absence of phagocytic ROS production leads to the development of CGD. Expression of Nox2 was also described in B lymphocytes, where the role of the enzyme is still poorly understood. Here, we show that peritoneal B cells, which were shown recently to possess phagocytic activity, have a high capacity to produce ROS in a Nox2-dependent manner. In phagocytosing B cells, intense intraphagosomal ROS production is detected. Finally, by studying 2 animal models of CGD, we demonstrate that phagocyte oxidase-deficient B cells have a reduced capacity to kill bacteria. Our observations extend the number of immune cell types that produce ROS to kill pathogens., (© Society for Leukocyte Biology.)

Background: Brucella spp. are intracellular bacteria that establish lifelong infections whose mechanisms of chronicity are poorly understood. Notably, B cells facilitate the establishment of the high infection plateau that persists for months., Methods: We evaluated the contribution of murine B cells toward providing infection niches for Brucella by using flow cytometry and microscopy and by determining live bacterial counts associated with B cells both in vivo and in vitro., Results: Herein we demonstrate that immunoglobulin M and complement-opsonized Brucella abortus infects and survives inside primary murine B cells protected from bactericidal effects of gentamicin. The entry was dependent on microfilaments for internalization and subsequently brucellae reside in a late endosomal/lysosomal compartment. Throughout the infection, 10% of colony-forming units from infected mice was associated with B cells, and these cells transferred disease to naive hosts. Furthermore, Brucella-positive cells were positive for transforming growth factor (TGF) β1, and about 10% of such cells were B cells, similar to rates found for other intracellular pathogens that induce their hosts cells to produce TGF-β1., Conclusions: To conclude, infected B cells contribute to chronic bacterial infections by providing an intracellular niche that may exert an immunoregulatory role. Although professional phagocytic cells harbor intracellular bacteria including Brucella, infection of lymphocytes by bacteria has not been previously appreciated.

Background: B cells positively contribute to immunity by antigen presentation to CD4(+) T cells, cytokine production, and differentiation into antibody secreting plasma cells. Accumulating evidence implies that B cells also possess immunoregulatory functions closely linked to their capability of IL-10 secretion., Methods: Colitis development was followed in CD4(+) CD25(-) T cell transplanted SCID mice co-transferred with B cells exposed to an enterobacterial extract (ebx-B cells). B and T cell cytokine expression was measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA)., Results: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-γ)-producing T(H) 1 cells and increased frequencies of Foxp3-expressing T cells., Conclusions: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

The gut mucosal immune system is crucial in host defense against infection by pathogenic microbacteria and viruses via the production of IgA. Previous studies have shown that intestinal commensal bacteria enhance mucosal IgA production. However, it is poorly understood how these bacteria induce IgA production and which genera of intestinal commensal bacteria induce IgA production effectively. In this study, we compared the immunomodulatory effects of Bacteroides and Lactobacillus on IgA production by Peyer's patches lymphocytes. IgA production by Peyer's patches lymphocytes co-cultured with Bacteroides was higher than with Lactobacillus. In addition, the expression of activation-induced cytidine deaminase increased in co-culture with Bacteroides but not with Lactobacillus. We found that intestinal commensal bacteria elicited IgA production. In particular, Bacteroides induced the differentiation of Peyer's patches B cell into IgA(+) B cells by increasing activation-induced cytidine deaminase expression.

A simple cytotoxicity assay for Listeria species was developed by assaying alkaline phosphatase (AP) release from an infected hybrid B lymphocyte (Ped-2E9) line. Eight of eight L. monocytogenes and six of 11 L. ivanovii strains induced significantly high AP release from Ped-2E9 cells compared to five other L. ivanovii strains and other Listeria spp. In contrast, all L. monocytogenes and L. ivanovii test strains showed high release of lactate dehydrogenase (LDH) activity from Ped-2E9 cells. The molecular mass of AP was estimated to be about 128-165 kDa, suggesting severe membrane damage in Ped-2E9 cells due to Listeria infection. The data presented here indicate that AP assay could be used over LDH assay to detect Listeria-induced cell cytotoxicity.

Lyme disease is a persistent low-density spirochetosis caused by Borrelia burgdorferi sensu lato. Although spirochetes causing Lyme disease are highly immunogenic in experimental models, the onset of specific antibody responses to infection is often delayed or undetectable in some patients. The properties and mechanisms mediating such immune avoidance remain obscure. To examine the nature and consequences of interactions between Lyme disease spirochetes and immune effector cells, we coincubated B. burgdorferi with primary and cultured human leukocytes. We found that B. burgdorferi actively attaches to, invades, and kills human B and T lymphocytes. Significant killing began within 1 hour of mixing. Cytopathic effects varied with respect to host cell lineage and the species, viability, and degree of attenuation of the spirochetes. Both spirochetal virulence and lymphocytic susceptibility could be phenotypically selected, thus indicating that both bacterial and host cell factors contribute to such interactions. These results suggest that invasion and lysis of lymphocytes may constitute previously unrecognized factors in Lyme disease and bacterial pathogenesis.

In enterobacteria-induced reactive arthritis (ReA), different T cell subsets play a role in the induction and maintenance of the synovitic process. Synovial fluid-derived alphabeta CD4, alphabeta CD8, and gammadelta T lymphocyte clones (TLC) that recognize Yersinia or Salmonella antigens on professional antigen-presenting cells (APC) have been characterized, and T cells themselves can function as nonprofessional APC. T cells were infected with the facultatively intracellular, arthritogenic enterobacterium Yersinia enterocolitica O:3. A CD8 TLC isolated from a patient with Yersinia-induced ReA recognized and efficiently lysed autologous and allogeneic Yersinia-infected T cells. Infected cytotoxic T lymphocytes (CTL) had a reduced lytic capacity against syngeneic and allogeneic infected target cells, suggesting that the infection of CTL by bacteria may represent a mechanism of immune escape. In ReA, antigen presentation by T cells may modify the antibacterial immune response and may also contribute to network control mechanisms of T cell-mediated cytotoxicity.

In a 79-year-old white woman, a lymphoproliferative disorder that was associated with type 2 Epstein-Barr virus (EBV) infection or reactivation, documented by three subsequent lymph node biopsies, was studied. After an initial phase with features of reactive lymphadenopathy with exhaustion of the follicular germinal centers and depletion of the B-cell lymphoid population, the disease evolved to a T-cell-rich lymphoma in which a clonal cell population of probable B-cell origin was identified. Such clonal cell population harbored the viral genome and expressed EBV latent membrane protein-1 but not EBV nuclear antigen-2. The implications of immunologic interactions between the clonal EBV-infected cells and the reactive T-cell component in the pathogenetic process are discussed.

Peripheral blood B cells from patients with systemic autoimmune disease and healthy volunteers were immortalized using EBV and the frequencies of B cell precursors that produced immunoglobulin class-specific antibodies against anti-nRNP, a specific marker for mixed connective tissue disease, were assessed using limiting dilution analysis. The frequencies of EBV-induced B cell precursors that produced IgG anti-nRNP were correlated closely with the serum titres of the corresponding autoantibodies, which indicates that B cell precursors that produced potentially pathogenic autoantibodies could be immortalized from the peripheral blood of the patients by EBV. In contrast, the frequency of EBV-induced B cell precursors that produced IgM anti-nRNP in patients with systemic autoimmune disease was comparable to that in healthy volunteers and greater than those that produced IgG and IgA anti-nRNP. Moreover, many of the clones that produced IgM antibodies against nRNP reacted with other autoantigens, such as double-stranded DNA, single-stranded DNA and rabbit IgG. These polyreactive IgM antibodies are believed to belong to the 'natural antibodies', to be coded by the germline immunoglobulin V genes, and to react with evolutionarily conserved structural cellular components, including nRNP. Our finding that nRNP is one of the target antigens for this polyreactive autoantibody may lead to the elucidation of the origin of the pathogenic IgG and IgA anti-nRNP antibodies found in sera from patients with systemic autoimmune diseases.

The structure-function relationships of the biological activities of mutant varieties of the pleiotropic cytokine interleukin-6 (human) were measured by three assays: induction of immunoglobulin M (IgM) secretion from an Epstein-Barr virus-transformed human B cell line and induction of fibrinogen secretion from either a human hepatoma cell line or a rat hepatoma cell line. The biological effects of the cytokine were characterized by three parameters as determined by a novel analysis: effectiveness (the maximal response attainable), efficiency (the concentration yielding a half-maximal response), and complexity (a measure of heterogeneity and feedback control). Substitution of serine for cysteine was associated with a reduction in the effectiveness of interleukin-6 in both fibrinogen secretion assays. In the assay with human hepatoma cells, there was also a profound reduction in efficiency. Serine substitution in the human IgM synthesis assay appears mainly to reduce the efficiency. Deletion of amino acids 4 to 23 increased the efficiency in the rat hepatoma assay. The complexity parameter suggests the presence of multiple receptor classes or negative feedback in all three assays. Use of the proposed sequential approach to the analysis of dose-response relations in bioassays provides a more useful quantitative assessment of activities as well as more insight into the complexity of the reactions.

The ability of baicalin (7-glucuronic acid, 5,6-dihydroxyflavone), a flavonoid compound purified from the Chinese medicinal herb, Scutellaria baicalensis georgi, to inhibit human T cell leukemia virus type I (HTLV-I) was examined. Baicalin produced concentration-dependent inhibition of HTLV-I replication in productively infected T and B cells. Moreover, baicalin treatment selectively reduced the detectable levels of HTLV-I p19 gag protein in infected cells by greater than 70% at concentrations that produced insignificant effects on total cellular protein and DNA synthesis with no loss in cell viability. Resistance to HTLV-I infection and virus-mediated transformation was noted in uninfected peripheral blood lymphocytes pretreated with baicalin before cocultivation with lethally irradiated chronically infected cells. Baicalin inhibited reverse transcriptase activity in HTLV-I-infected cells as well as the activity of purified reverse transcriptase from Moloney murine leukemia virus and Rous-associated virus type 2. These results suggest that baicalin may be a potential therapeutic agent against HTLV-I-associated T cell diseases.

Persistent generalized lymphadenopathy (PGL) and polyclonal B cell activation are features of infection with HIV. Epstein-Barr virus (EBV) and HIV are known to activate B cells in vitro, but whether they are important B cell activators in patients infected with HIV is less clear. In this study, lymph node tissue was obtained from 10 patients with PGL and assessed for evidence of EBV and HIV gene sequences. DNA was extracted and specific viral gene sequences identified using the polymerase chain reaction (PCR). EBV sequences were difficult to detect in the PGL tissue, with a signal intensity similar to that of other benign and malignant lymphoid conditions not associated with EBV. HIV sequences were also rare in the PGL tissue, consistent with HIV infection of the small number of peripheral blood cells and nodal T cells likely to be present in such a sample. These findings suggest that the polyclonal B cell activation typical of HIV is not driven by direct EBV or HIV infection of B cells.

A nonisotopic, in situ hybridization procedure is described for detecting Epstein-Barr viral (EBV) DNA in cytopreparations of pepsin-digested, unfixed cells in less than 3 hours. The procedure, which uses an EBV Bam HI W DNA probe conjugated directly to horseradish peroxidase, first was optimized using an EBV-infected cell line (ARH-77) and then validated on four positive control specimens and six negative control specimens. Optimization studies demonstrated distinct nuclear hybridization signal in less than 10% of formaldehyde-fixed, pepsin-digested ARH-77 cells. When formaldehyde fixation was omitted, more than 50% of the pepsin-digested ARH-77 cells had strong nuclear staining. Unfixed cells from the four positive controls had detectable hybridization signal; the presence of EBV-DNA in these specimens also was confirmed by a polymerase chain reaction. There was no hybridization signal in the six negative control specimens. The results indicate that this nonisotopic, in situ hybridization procedure rapidly detects the presence of EBV-DNA in cytopreparations of unfixed, pepsin-digested cells from clinical specimens. There is a tradeoff, however, between assay sensitivity and preservation of cytologic details.

We studied the cellular function and lymphokine production of T cells from patients with X-linked lymphoproliferative disease (XLP) when activated by the challenge with Epstein-Barr virus (EBV) infection. We used an assay system in which T cells were stimulated with membrane antigens of autologous EBV-infected B lymphoblastoid cell lines (B-LCL) and we examined cellular and humoral factors derived from the stimulated T cells which control the growth of EBV-infected B-LCL. Immunoglobulin secretion from the autologous B-LCL was suppressed with radiosensitive suppressor cells in the patients with XLP. The degree of suppression was correlated with the immunoglobulin levels in the serum of the patients with acquired hypogammaglobulinaemia (P less than 0.05). In addition, T cells from the patients with XLP failed to produce interferon-gamma (IFN-gamma) (P less than 0.001). Moreover, the T cell supernatants from the patients with XLP were less potent to inhibit the B-LCL growth. This diminished inhibition of the B-LCL growth was correlated well with the decreased concentration of IFN-gamma in the T cell supernatants. These findings suggest that suppressor cells may be activated in the patients with the hypogammaglobulinaemia phenotype of XLP, but the frequent development of B cell lymphoma in hypogammaglobulinaemia indicate that immunoglobulin suppression may not exert enough pressure on the in vivo growth of EBV-infected B cells. The defective secretion of IFN-gamma may be, at least partially, responsible for the abnormal cytotoxic T cell and natural killer activities found in the patients with XLP, and may indicate the clinical evaluation about the preventive injection of IFN-gamma against the development of malignant lymphoma.

The number of varicella zoster virus-infected mononuclear cells in blood samples obtained during 3 days before appearance of vesicular skin rashes could be estimated in 13 of 21 immunocompetent children with varicella and viremia (range, 1-83 per 10(7) mononuclear cells). The virus was isolated from 5% of adherent cells (1/21), 71% of nonadherent cells (12/17), 43% of T lymphocytes (9/21), and 33% of B lymphocytes (7/21). The number of vesicles on the body correlated with the maximum body temperature, duration of fever, and number of infected cells in the blood. These results indicate that varicella zoster virus infection in immunocompetent children is disseminated by circulating T and B lymphocytes and the severity of the viremia is reflected in the severity of the disease.

The role of a macrophage-enriched subpopulation in acute intraperitoneal infection of mice with cytomegalovirus was investigated. Virus was not detectable in extracellular fluid after the first day, but it could be isolated from peritoneal exudate cells for at least three weeks after infection. The virus was found in adherent and nonadherent cells after plastic-adherence separation. Infection of recipient mice was achieved by adoptive transfer of either subpopulation two or 21 days after infection. Further study of the macrophage-enriched adherent subpopulation revealed no evidence of significant viral replication. Pretreatment of mice to activate macrophages did not impair dissemination of the virus. Thus, cytomegalovirus can infect a subpopulation of cells enriched in macrophages, and although little replication occurs, such infection facilitates the establishment of persistent infection.

Peripheral blood lymphocytes from 3 cows with persistent lymphocytosis were separated on nylon wool columns into nylon wool-adherent and nonadherent populations. The percentage of cells coated with surface immunoglobulin (B-cells) and the frequency of lymphocytic nuclear pockets in each sub-population were then determined. In each case the adherent population consisted predominantly of B-cells with an increased nuclear pocket frequency, whereas the nonadherent cells were 98.99% negative for surface immunoglobulin (non-B-cells) and contained essentially no nuclear pockets. These findings provided additional evidence that the B-subpopulation of cells was highly involved in bovine leukemia oncogenesis.

The number of plaque-forming units (PFU) from lymphocytes latently infected with oncogenic (GA-5) or nononcogenic (SB-1) Marek's disease virus (MDV) was decreased after complement lysis with antisera against thymus-derived lymphocytes or bursa-derived lymphocytes; an additive effect with dual treatment was observed. Complement lysis with antisera against Marek's disease tumor-associated surface antigen (putative tumor antigen) had little effect, which suggests an absence of the antigen on latently infected cells. None of the serum complement treatments affected the number of PFU from lymphocytes infected with turkey herpesvirus (HVT). No viral antigens were detected in spleen lymphocytes when removed from infected birds. After 42-72 hours of incubation, many cultured spleen cells from MDV-infected birds (JM-10, GA-5, and SB-1 isolates) contained viral antigen, whereas very few if any cultured cells from HVT-infected birds were positive. These data suggest that the nature of the latent infections with MDV and HVT may differ significantly.

How 3'-azido-3'-deoxythymidine (AZT) affects the ability of three different variants of HIV-1 to infect a line of EBV-transformed B cells was studied. Susceptible cells were pretreated with three different concentrations of AZT (1, 5, and 10 microM) for 4 h before viral inoculation and were maintained after infection in drug-containing medium. Establishment of viral infection was assessed by indirect immunofluorescence for viral antigens and by antigen capture assay carried out on culture fluids. AZT completely blocked infection in one of the HIV-1 variants studied; in the other two, treatment of cells with AZT significantly delayed the appearance of progeny virus.

Epstein-Barr virus (EBV) is the human prototype of a family of closely related herpesviruses of Old World primates. These agents probably evolved and spread among the Old World primates since the divergence of apes from monkeys about 30 million years ago. Although the DNAs of the EBV family have no sequence homology to other herpesviruses, there are some features in common with other herpesviral genomes. EBV DNA is unusual in having five tandem direct repeat elements which divide the genome into five unique sequence domains. The tandem direct repeats at the ends of the linear virion DNA probably mediate circularization of the viral DNA to form the circular episomal viral DNA which is characteristic of EBV-infected cells. In latent transforming infection, messenger RNAs are encoded by three widely separate regions of the EBV genome. The remainder of the viral genome encodes many RNAs and proteins which are expressed in productive infection. Early and late viral genes are intermixed along the full length of EBV DNA.

Bovine peripheral blood lymphocytes (PBL's) from 3 cows and 1 steer infected with bovine leukemia virus (BLV) were separated by fractionation through nylon wool columns into nylon-adherent and nonadherent cell populations. Nylon-adherent cells were enriched in B-lymphocytes, as determined by the presence of surface membrane immunoglobulins (slg), whereas nylon-nonadherent cells or "non-B-lymphocytes" contained few slg-bearing cells. PBL's and separated B- and non-B-lymphocyte populations were assayed for the presence of BLV by the induction of syncytia in bovine embryonic spleen cells. PBL's and B-lymphocyte populations both produced many syncytia, whereas non-B-lymphocytes yielded few or no syncytia. The specificity of syncytia formation by anti-BLV serum. PBL's from 2 control animals were negative for syncytia induction. This study presents further evidence that B-lymphocytes are the target cells for BLV infection.

Freshly isolated human B-lymphocytes from eight subjects and Epstein-Barr virus-transformed human B-lymphocytes from seven subjects were examined for their capacity to secrete insulin-like growth factor-I (IGF-I) and IGF-II and for their capacity to respond to human GH. Similar studies were conducted with Epstein-Barr virus-transformed lymphocytes collected from six African pygmies. When transformed B-lymphocytes from normal stature subjects were cultured for 3 weeks in RPMI-1640 medium (6 x 10(3) cells/75-cm2 flask at seeding), significant amounts of IGF-I, but no IGF-II, were produced. GH (150 ng/mL) significantly increased for control cells the amount of IGF-I produced at each sampling interval compared to that by unstimulated cultures (P less than 0.05 at 1 week; P = 0.005 at 3 weeks). At 3 weeks, cell counts of cultures compared were 4.13 +/- 0.39 X 10(6)/mL for unstimulated cells and 4.23 +/- 0.87 X 10(6)/mL for GH-stimulated cells. IGF-I production at this time interval by unstimulated cells was 2.8 +/- 2.3 ng/mL, and that by GH-stimulated cells was 12.3 +/- 2.5 ng/mL (P = 0.005). Cell multiplication rates of control cultures were increased in 1 week by GH stimulation [GH stimulated, [16.7 +/- 22.0 X 10(4) cells, unstimulated, 5.73 +/- 4.1 X 10(4) cells; (mean +/- SD); n = 14; P less than 0.01]. Similar results occurred with GH studied at a lower concentration of 10 ng/mL for 3 weeks. Freshly isolated B-lymphocytes did not secrete IGF-I and II after 5 days of culture with GH. Cultures established from cells derived from pygmies produced significantly less IGF-I (4.24 +/- 2.62 ng/mL) when stimulated with 150 ng/mL GH than cultures of cells from normal stature subjects (12.3 +/- 2.5 ng/mL; 0.005 less than P less than 0.01). The cultures compared had a similar cell density. A similar significant difference in IGF-I secretion occurred between cultures of pygmy and control cells stimulated with 10 ng/mL GH. These data are consistent with previous in vivo studies in which pygmies failed to increase IGF-I and exhibit metabolic responses to exogenous GH.

Circulating lymphocytes from squirrel monkeys persistently infected with Herpesvirus saimiri (HVS) were separated into B- and T-lymphocyte fractions by a rosette-enrichment technique. HVS was isolated only from lymphocyte fractions forming rosettes or from unseparated lymphocytes; this indicated that T-lymphocytes were the target cells for HVS in the natural host, squirrel monkeys.

A human B-cell line designated as BALL-1 was established from the peripheral blood of a patient with acute lymphoblastic leukemia (ALL). Neither Epstein-Barr virus (EBV) particles nor EBV-determined nuclear antigen (EBNA) was detectable. The morphologic and growth characteristics were clearly distinct from those of numerous EBV-positive lymphoblastoid cell lines previously reported. BALL-1 cells probably originated from the donor's leukemia cells as judged from their cytogenetic, morphologic, and surface features. The BALL-1 line was the first EBNA-negative B-cell line established from ALL.