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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03222010-134114 |
| Date | 23 March 2010 |
| Creators | Kuhrt, David Michael |
| Contributors | Lisa Borghesi, Todd Reinhart, Kelly Stefano Cole, Christine Milcarek, Karen Norris |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-03222010-134114/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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