Epstein Barr Virus Transformation of Peripheral Blood B Cells Secreting Antibodies Reactive with Cell Surface Antigens

When Epstein-Barr virus (EBV) infects B cells in vitro, the result is a proliferating lymphoblast that expresses at least nine latent proteins. It is generally believed that these cells are rigorously controlled in vivo by cytotoxic T cells. Consistent with this, the latently infected cells in the peripheral blood of healthy carriers are not lymphoblasts. Rather, they are resting memory B cells that are probably not subject to direct immunosurveillance by cytotoxic T lymphocytes (CTLs). When patients become immunosuppressed, the viral load increases in the peripheral blood. The expansion of proliferating lymphoblasts due to the suppressed CTL response is believed to account for this increase and is considered to be a major risk factor for posttransplant lymphoproliferative disease (PTLD) and AIDS-associated B cell lymphoma. Here we show that there is an increase in the numbers of latently infected cells in the peripheral blood of immunosuppressed patients. However, the cells are not proliferating lymphoblasts. They are all latently infected, resting, memory B cells—the same population of infected cells found in the blood of healthy carriers. These results are discussed in the context of a model for EBV persistence that explains why PTLD is usually limited to the lymph nodes.

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Epstein-Barr virus transformation of Saimiri sciureus (squirrel monkey) B cells and generation of a Plasmodium brasilianum-specific monoclonal antibody in P. brasilianum-infected monkeys.

Infection and Immunity ◽

10.1128/iai.59.7.2285-2290.1991 ◽

1991 ◽

Vol 59 (7) ◽

pp. 2285-2290 ◽

Cited By ~ 2

Author(s):

C Chizzolini ◽

A J Sulzer ◽

M A Olsen-Rasmussen ◽

W E Collins

Keyword(s):

Monoclonal Antibody ◽

B Cells ◽

Squirrel Monkey ◽

Epstein Barr Virus ◽

Saimiri Sciureus ◽

Specific Monoclonal Antibody ◽

Barr Virus ◽

Virus Transformation ◽

Epstein Barr ◽

Plasmodium Brasilianum

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Expression of Epstein-Barr Virus BamHI-A Rightward Transcripts in Latently Infected B Cells From Peripheral Blood

Blood ◽

10.1182/blood.v93.9.3026.409k28_3026_3032 ◽

1999 ◽

Vol 93 (9) ◽

pp. 3026-3032 ◽

Cited By ~ 7

Author(s):

Honglin Chen ◽

Paul Smith ◽

Richard F. Ambinder ◽

S. Diane Hayward

Keyword(s):

B Cells ◽

Peripheral Blood ◽

Epstein Barr Virus ◽

Open Reading Frames ◽

Viral Gene ◽

Barr Virus ◽

Restricted Form ◽

Latently Infected ◽

Epstein Barr

In addition to the Epstein-Barr virus (EBV) EBNA and LMP latency genes, there is a family of alternatively spliced BamHI-A rightward transcripts (BARTs). These latency transcripts are highly expressed in the EBV-associated malignancies nasopharyngeal carcinoma and Burkitt’s lymphoma, and are expressed at lower levels in latently EBV-infected B-cell lines. The contribution of the BARTs to EBV biology or pathogenesis is unknown. Resting B cells have recently been recognized as a reservoir for EBV persistence in the peripheral blood. In these cells, EBV gene expression is tightly restricted and the only viral gene known to be consistently expressed is LMP2A. We used cell sorting and reverse-transcriptase polymerase chain reaction (RT-PCR) to examine whether BARTs are expressed in the restricted form of in vivo latency. Our results demonstrated that RNAs with splicing diagnostic for transcripts containing the BART RPMS1 and BARFO open-reading frames (ORFs) were expressed in CD19+ but not in CD23+ B cells isolated from peripheral blood of healthy individuals. The product of the proximal RPMS1 ORF has not previously been characterized. The RPMS1 ORF was shown to encode a 15-kD protein that localized to the nucleus of transfected cells. Expression of the BARTs in peripheral blood B cells suggests that the proteins encoded by these transcripts are likely to be important for maintenance of in vivo latency.

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Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells.

Journal of Experimental Medicine ◽

10.1084/jem.157.1.1 ◽

1983 ◽

Vol 157 (1) ◽

pp. 1-14 ◽

Cited By ~ 79

Author(s):

R Yarchoan ◽

G Tosato ◽

R M Blaese ◽

R M Simon ◽

D L Nelson

Keyword(s):

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Epstein Barr Virus ◽

Cell Activation ◽

B Cell Activation ◽

Barr Virus ◽

Human B Cells ◽

Epstein Barr ◽

Limiting Dilution

The Epstein-Barr virus (EBV) is a herpes virus that has the capacity to infect human B cells and to induce them to secrete immunoglobulin (Ig). In the current experiments, Poisson analysis of limiting dilution cultures has been used to study the activation of human peripheral B cells by the B95-8 strain of EBV. Under the culture conditions used, 0.2-1% of peripheral blood B cells were activated by EBV to secrete IgM or IgG. In addition, when multiple replicate cultures containing limited numbers of B cells were tested for IgM and for IgG production, the precursors for IgM and IgG segregated independently; thus, individual B cell precursors matured into cells secreting IgM or IgG but not both classes of Ig. Additional experiments using limiting dilutions of EBV were undertaken to study the viral requirements for B cell activation. These studies indicated that B cell activation by EBV to produce Ig was consistent with a "one-hit" model and inconsistent with a "two-hit" model. Taken together, these results indicate that infection by one EBV virion is sufficient to induce a precursor peripheral blood B cell to secrete Ig and that only one isotype of Ig is then secreted.

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