Saturday, 15 September 2012

Research: EBV persistence in B cells

Epub: Tracy et al. Persistence of Epstein-Barr Virus in Self-reactive Memory B Cells. J Virol. 2012 Sep 5.

Epstein-Barr virus (EBV) infection is epidemiologically associated with the development of multiple autoimmune diseases, particularly systemic lupus erythematosus (SLE) and MS.

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 virally encoded LMP1 and LMP2a proteins, which act as functional homologues of CD40 (co-stimulatory molecule) 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, these investigators cloned and expressed antibodies from EBV+ and EBV- memory B cells present during acute infection and profiled their self and polyreactivity. 


GC = germinal centre
"The germinal centre refers to a unique structure within lymph nodes, spleen and other immune structures where B cells mature and design their antibodies to be high highly selective to whatever protein they react with. If you understand biology and immunology you will appreciate how beautiful, and extraordinary, this process is!"
A cartoon explaining how B clell mature in the germinal centre.

They found that EBV does persist within self and polyreactive B cells, but found no evidence that it favoured 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. This 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. They suggest this might reflect an active process of the virus to minimize the risk of autoimmune disease


"This paper questions one of the hypotheses put forward the EBV causes MS by immortalising autoreactive B cells, i.e. B cells that produce antibodies against self or B cells that stimulate T cells,  to attack self proteins that these antibodies bind to."

"One of the unsolved mysteries in MS is how and when does EBV trigger MS? What is the biology of this process? If we understood this we could target this process or processes to treat or prevent MS."

3 comments:

  1. RE _ "If you understand biology and immunology you will appreciate how beautiful, and extraordinary, this process is!"

    The way you phrase that is almost like an astrologer describing the wonders of the celestial cosmos. I guess the human body holds as many wonders and mysteries as the universe.

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  2. Yes Prof G is doing a Brian Cox ..its amazing its all made out of starrrrdust :-)

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  3. "I guess the human body holds as many wonders and mysteries as the universe"

    The difference is the main mysteries of the human body will get worked out....the mysteries of the universe will be conjecture

    ReplyDelete

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