Stat3 Is Important For The Emergence Of Human B Cells Predicted To Proliferate After Infection With Epstein-Barr Virus

Author

Amanda Victoria Zeta De La Paz, Yale School of MedicineFollow

Date of Award

January 2011

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Sumita Bhaduri-McIntosh

Subject Area(s)

Medicine, Immunology

Abstract

STAT3 is important for the emergence of human B Cells predicted to proliferate after infection with Epstein-Barr Virus

Amanda Z. de la Paz and Sumita Bhaduri-McIntosh. Section of Infectious Diseases, Department of Pediatrics, Yale University, School of Medicine, New Haven, CT.

Many unanswered questions surround the early changes in B cells that lead to establishment of latency and immortalization following Epstein-Barr virus (EBV) infection. Data from the Bhaduri-McIntosh lab revealed that EBV differentially infects B cells into distinct sub-populations, only one of which, those marked CD23hi CD58+ IL6-, can be predicted to proliferate as early as 3 days after exposure to EBV. Other cells produced IL6 but did not proliferate, perhaps assisting a select few to do so. They also found that high levels of signal transducer and activator of transcription 3 (STAT3) correlate with resistance to lytic cycle induction and hence maintenance of the immortalized state. We hypothesized that 1) IL6 is necessary for the emergence of CD23hi CD58+ B cells following infection with EBV, and that 2) phosphorylation of STAT3 is necessary for the emergence of this B cell sub-population that is predicted to proliferate. We tested these hypotheses and showed that blocking IL6 by infecting human primary B cells with EBV in the presence of neutralizing antibodies did not have an effect on the emergence of CD23hi CD58+ cells. However, the STAT3 inhibitors Stattic and AG490, abrogated the emergence of this sub-population, especially within 24 hours of exposure to EBV. We concluded that phosphorylation of STAT3 is important for the emergence of human B cells predicted to proliferate during the process of immortalization after EBV infection.

Comments

This is an Open Access Thesis.

Recommended Citation

De La Paz, Amanda Victoria Zeta, "Stat3 Is Important For The Emergence Of Human B Cells Predicted To Proliferate After Infection With Epstein-Barr Virus" (2011). Yale Medicine Thesis Digital Library. 1547.
https://elischolar.library.yale.edu/ymtdl/1547