Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells

被引:35
作者
Al Tabaa, Yassine [1 ]
Tuaillon, Edouard [1 ]
Bollore, Karine [1 ]
Foulongne, Vincent [1 ]
Petitjean, Gael [1 ]
Seigneurin, Jean-Marie [2 ]
Duperray, Christophe [3 ]
Desgranges, Claude [4 ,5 ]
Vendrell, Jean-Pierre [1 ,3 ]
机构
[1] Univ Med Ctr, Dept Virol, F-34295 Montpellier, France
[2] Univ Med Ctr, Dept Virol, Grenoble, France
[3] INSERM, U847, Montpellier, France
[4] Univ Paris 05, CNRS, UMR 8104, Inst Cochin, F-75270 Paris, France
[5] INSERM, U567, Paris, France
关键词
ORGAN TRANSPLANT RECIPIENTS; ANTIBODY-SECRETING CELLS; IMMEDIATE-EARLY GENE; IN-VIVO; LYMPHOPROLIFERATIVE DISEASE; LYTIC REPLICATION; ELISPOT ASSAY; BZLF1; GENE; LYMPHOCYTES; CD27;
D O I
10.1182/blood-2008-02-136903
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes latency in resting memory B lymphocytes, and is involved in oncogenesis through poorly understood mechanisms. The EBV lytic cycle is initiated during plasma cell differentiation by mRNAs transcripts encoded by BZLF1, which induce the synthesis of EBV proteins such as the immediate-early antigen ZEBRA and the late membrane antigen gp350. Therefore, we assessed the capacity of circulating EBV-infected B lymphocytes from healthy EBV-seropositive subjects to enter and complete the EBV lytic cycle. Purified B lymphocytes were polyclonally stimulated and BZLF1- or gp350-secreting cells (BZLF1-SCs or gp350-SCs) were enumerated by ELISpot assays. The number of BZLF1-SCs ranged from 50 to 480/107 lymphocytes (median, 80; 25th-75th percentiles, 70-150) and gp350-SCs from 10 to 40/107 lymphocytes (median, 17; 25th-75th percentiles, 10-20). gp350-SCs represented only 7.7% to 28.6% of BZLF1-SCs (median, 15%; 25th-75th percentiles, 10.5%-20%). This EBV functional reservoir was preferentially restricted to plasma cells derived from CD27(+) IgD(-) memory B lymphocytes. In 9 of 13 subjects, EBV DNA quantification in B-cell culture supernatants gave evidence of completion of EBV lytic cycle. These results demonstrate that EBV proteins can be secreted by EBV-infected B lymphocytes from healthy carriers, a majority generating an abortive EBV lytic cycle and a minority completing the cycle. (Blood. 2009; 113: 604-611)
引用
收藏
页码:604 / 611
页数:8
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