Reversal of EBV immortalization precedes apoptosis in IL-6-induced human B cell terminal differentiation.

TitleReversal of EBV immortalization precedes apoptosis in IL-6-induced human B cell terminal differentiation.
Publication TypeJournal Article
Year of Publication1997
AuthorsAltmeyer A, Simmons RC, Krajewski S, Reed JC, Bornkamm GW, Chen-Kiang S
Date Published1997 Nov
KeywordsAnimals, Apoptosis, B-Lymphocytes, Callithrix, Cell Differentiation, Cell Transformation, Viral, Cells, Cultured, Epstein-Barr Virus Nuclear Antigens, G1 Phase, Gene Expression Regulation, Viral, Herpesvirus 4, Human, Humans, Interleukin-6, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins, Plasma Cells, Proto-Oncogene Proteins c-bcl-2, Viral Matrix Proteins

Cell death in B cell terminal differentiation rapidly follows cell cycle arrest in IL-6 differentiation of EBV-immortalized, IgG-bearing human lymphoblastoid cells in vitro. G1 arrest is now found to coincide with repression of EBNA2 and LMP1, two EBV genes essential for B cell transformation, without activation of the viral lytic cycle. IL-6-differentiated B cells die by apoptosis, as evidenced by increases in Annexin V binding activity, PARP cleavage, and chromatin disorganization. Expression of Mcl-1, a Bcl-2 family member, was specifically induced during IL-6 differentiation and down-regulated during apoptosis. Thus, IL-6 reverses EBV immortalization and activates the terminal differentiation program in IgG-bearing human B lymphoblastoid cells, including regulation of an anti-apoptotic gene to coordinate differentiation, cell cycle arrest, and cell death.

Alternate JournalImmunity
PubMed ID9390690
Grant ListAR44580 / AR / NIAMS NIH HHS / United States
CA69381 / CA / NCI NIH HHS / United States
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Related Faculty: 
Selina Chen-Kiang, Ph.D.

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