Persistence of epstein-barr virus in self-reactive memory B cells
Department of Pediatrics
Medical Subject Headings
B-Lymphocytes; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Immunologic Memory
Immunology and Infectious Disease
Epstein-Barr virus infection has been epidemiologically associated with the development of multiple autoimmune diseases, particularly systemic lupus erythematosus and multiple sclerosis. Currently, there is no known mechanism that can account for these associations. The germinal-center (GC) model of EBV infection and persistence proposes that EBV gains access to the memory B cell compartment via GC reactions by driving infected cells to differentiate using the virus-encoded LMP1 and LMP2a proteins, which act as functional homologues of CD40 and the B cell receptor, respectively. The ability of LMP2a, when expressed in mice, to allow escape of autoreactive B cells suggests that it could perform a similar role in infected GC B cells, permitting the survival of potentially pathogenic autoreactive B cells. To test this hypothesis, we cloned and expressed antibodies from EBV(+) and EBV(-) memory B cells present during acute infection and profiled their self- and polyreactivity. We find that EBV does persist within self- and polyreactive B cells but find no evidence that it favors the survival of pathogenic autoreactive B cells. On the contrary, EBV(+) memory B cells express lower levels of self-reactive and especially polyreactive antibodies than their uninfected counterparts do. Our work suggests that EBV has only a modest effect on the GC process, which allows it to access and persist within a subtly unique niche of the memory compartment characterized by relatively low levels of self- and polyreactivity. We suggest that this might reflect an active process where EBV and its human host have coevolved so as to minimize the virus's potential to contribute to autoimmune disease.
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Citation: J Virol. 2012 Nov;86(22):12330-40. doi: 10.1128/JVI.01699-12. Epub 2012 Sep 5. Link to article on publisher's site
Tracy, Sean I.; Kakalacheva, Kristina; Lunemann, Jan D.; Luzuriaga, Katherine; Middeldorp, Jaap M.; and Thorley-Lawson, David A., "Persistence of epstein-barr virus in self-reactive memory B cells" (2012). Pediatric Publications and Presentations. 20.