The effect of hepatitis B virus e protein on B lymphocytes

• Main Authors: Po-chun Li, 李柏鈞
• Other Authors: Cheng-po Hu
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/72972279709797803751

碩士 === 東海大學 === 生命科學系 === 99 === Hepatitis B virus (HBV) infects human liver cells and may cause acute or chronic infection. Up to the present, the reason why HBV causes chronic infection is largely unknown. Hepatitis B virus e protein (HBe) is a nonstructural protein which is neither required for viral replication nor for viral infection. However, the woodchuck hepatitis B virus with the e deletion could not cause chronic infection in newborn woodchucks; and the ducks infected with duck hepatitis B virus with the e mutation produced an increased amount of anti-core antibodies. These findings suggest that HBe may exert an immunomodulatory function in the host. Previously, our laboratory found that HBe could bind human and mouse monocytes and B lymphocytes. HBe was shown to suppress the respiratory burst of monocytes and to modulate the secretion of cytokines/chemokines from monocytes. My thesis’ focus is on the effect of HBe on mouse B lymphocytes. I found that HBe could induce the expression of activation molecules on resting B lymphocytes, such as CD19, CD21, CD69, CD80, CD86, MHC I, MHC II and sIgM, and the cell size were increased. Since these molecules are crucial for B cell activation, HBe may affect some functions of B cells. To understand whether HBe could affect the antigen-stimulated B cells, I used anti-IgM plus anti-CD40 antibodies to crosslink B cell receptors for activation. Under the stimulation of anti-IgM plus anti-CD40, CD19, CD69, CD86, MHC I and MHC II molecules were upregulated as expected. When HBe was added into the culture, the anti-IgM- plus anti-CD40-induced expression of CD19, CD69, CD86 and MHC I were further increased on B cells. On the contrary, the induction of MHC II molecules was downregulated in the presence of the HBe protein. This HBe-inhibited MHC II expression is specific for anti-IgM- plus anti-CD40-activated B cells because HBe does not suppress the expression of MHC II on LPS-activated B cells. During HBV infection, a suppressive effect of HBe on the induction of MHC II on activated B cells may result in the incomplete activation and/or differentiation of HBV-specific B cells and downregulation of anti-HBV neutralizing antibodies. This study may shed light on the understanding of the immune tolerance during HBV infection.