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SIV infection results in detrimental phenotypic and functional alterations of the naive and memory B cell compartments that are initiated during acute infection

Kuhrt, David Michael (2010) SIV infection results in detrimental phenotypic and functional alterations of the naive and memory B cell compartments that are initiated during acute infection. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Multiple B cell abnormalities have been described in humans infected with HIV. These abnormalities include hypergammaglobulinaemia, diminished B cell response to mitogenic stimuli, lymphoma and a depletion of the memory B cell population. There is also evidence to suggest that B cells in HIV infected patients are functionally impaired. The initial antibody response to HIV infection is slow to appear and antibody responses to B cell mediated vaccines in HIV infected individuals are less robust and less durable than in uninfected individuals. Although B cell abnormalities have been characterized in humans, efforts to link these abnormalities to a specific defect within the B cell compartment have not been entirely successful. The SIV/macaque model of HIV infection of humans provides a means for addressing questions about the naïve and memory B cell populations, whose activity may be differentially compromised by HIV infection, but lacking is the ability to resolve these functionally relevant B cell populations in the rhesus macaque. In this study, we established CD27 as a definitive memory B cell marker in the rhesus macaque. Further, we demonstrated that the naïve and memory B cell populations are depleted from the periphery within 14 days of SIV infection and that the memory B cell population recovered more quickly. We also showed that chronic SIV infection resulted in a loss of CD40 mediated naïve B cell survival, indicating a potential mechanism through which SIV infection may lead to the production of non-reactive or self reactive antibody producing cells. Together, these findings demonstrated that B cell dysfunctions associated with SIV infection are not limited to the memory B cell population as previously thought, but rather that naïve B cell deficits may be more severe than what has been observed in the memory compartment. Increased focus on abrogating alterations that occur within the naïve compartment have the potential to improve viral control in infected individuals. This study of phenotypic and functional B cell changes over the course of infection will aid in the development of strategies that have the potential to improve prophylactic and therapeutic B cell mediated vaccine efficacy.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Kuhrt, David Michaeldmk26@pitt.eduDMK26
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairStefano Cole, Kellystefcole@pitt.eduSTEFCOLE
Committee MemberMilcarek, ChristineMilcarek@pitt.eduMILCAREK
Committee MemberNorris, Karenkan1@pitt.eduKAN1
Committee MemberBorghesi, Lisaborghesi@pitt.eduBORGHESI
Committee MemberReinhart, Toddreinhar@pitt.eduREINHAR
Date: 23 March 2010
Date Type: Completion
Defense Date: 18 February 2010
Approval Date: 23 March 2010
Submission Date: 22 March 2010
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Virology and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: HIV; B cells; SIV
Other ID:, etd-03222010-134114
Date Deposited: 10 Nov 2011 19:32
Last Modified: 15 Nov 2016 13:37


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