Humoral immunity constitutes major defense mechanism against viral infections. However, the association of hepatic injury and B-cells population in chronic hepatitis B virus (HBV) carriers has not been studied well. In this study, fifty seven hepatitis B surface antigen (HBsAg) positive and HBeAg negative patients were studied to determine the expression of CD20, a cell surface marker expressed on B-cells, in liver biopsy sections using immunohistochemistry. The patients’ clinical data at the time of liver biopsy were acquired from their medical records. There was a significant association between log HBV DNA and both ALT ( , ) and histologic activity index (HAI) total score ( , ), respectively. The CD20 was expressed in all 57 liver biopsy samples with a submembranous and membranous staining pattern and its expression was significantly associated with HAI total score ( , ) and stage of fibrosis ( , ). The susceptible B lymphocytes to hepatitis B virus might be implicated in the development of immune mediated inflammation of HBV-induced hepatic injury. The present data also support that the liver is potentially one of the secondary lymphoid organs. 1. Introduction Chronic hepatitis B (CHB) virus (HBV) infection is the principal cause of cirrhosis and hepatocellular carcinoma (HCC) [1]. The pathogenesis of HBV-related chronic liver disease is not well understood. However, it is clear that the immune mechanisms associated with the antiviral response are responsible for CHB outcome [2–4]. The existence of lymphocytes in the human liver is representing a pathological situation [5]. This concept stems from the observation that, in chronic hepatitis B, T-cells can potentially participate both in the immune clearance of HBV-infected cells and in the pathogenesis of hepatocellular injury [6]. Furthermore the numbers of B lymphocytes and plasma cells are significantly higher in patients with liver cirrhosis than of those with inactive chronic hepatitis [7, 8]. Enormous intrahepatic B-cells with massive production of IgM and IgG and infiltrating plasma cells into the hepatic lobules have also been shown in HBV-associated chronic active hepatitis [9]. B-cells contribute to immune responses through the secretion of effector cytokines and it has been suggested that naive and memory B-cell subsets preferentially produce different effector cytokines [10, 11]. Na？ve B-cells undergo maturation by somatic hypermutation in immunoglobulin variable region of the B-cell receptor (BCR) genes following contact with a specific protein accessible on dendritic cells. Then the
References
[1]
G. Montazeri, “Current treatment of chronic hepatitis B,” Archives of Iranian Medicine, vol. 9, no. 1, pp. 1–10, 2006.
[2]
A. Mohamadkhani, M. Sotoudeh, S. Bowden et al., “Downregulation of HLA class II molecules by G1896A pre-core mutation in chronic hepatitis B virus infection,” Viral Immunology, vol. 22, no. 5, pp. 295–300, 2009.
[3]
H. Poustchi, A. Mohamadkhani, S. Bowden et al., “Clinical significance of precore and core promoter mutations in genotype D hepatitis B-related chronic liver disease,” Journal of Viral Hepatitis, vol. 15, no. 10, pp. 753–760, 2008.
[4]
M. A. Aller, I. Prieto, S. Argudo et al., “The interstitial lymphatic peritoneal mesothelium axis in portal hypertensive ascites: when in danger, go back to the sea,” International Journal of Inflammation, vol. 2010, Article ID 148689, 2010.
[5]
A. P. Holt, E. L. Haughton, P. F. Lalor, A. Filer, C. D. Buckley, and D. H. Adams, “Liver myofibroblasts regulate infiltration and positioning of lymphocytes in human liver,” Gastroenterology, vol. 136, no. 2, pp. 705–714, 2009.
[6]
M. Iannacone, G. Sitia, and L. G. Guidotti, “Pathogenetic and antiviral immune responses against hepatitis B virus,” Future Virology, vol. 1, pp. 189–196, 2006.
[7]
B. Oliviero, A. Cerino, S. Varchetta et al., “Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections,” Journal of Hepatology, vol. 55, no. 1, pp. 53–60, 2011.
[8]
F. Marra, S. Aleffi, S. Galastri, and A. Provenzano, “Mononuclear cells in liver fibrosis,” Seminars in Immunopathology, vol. 31, no. 3, pp. 345–358, 2009.
[9]
P. Farci, G. Diaz, Z. Chen et al., “B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 19, pp. 8766–8771, 2010.
[10]
M. Duddy, M. Niino, F. Adatia et al., “Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis,” Journal of Immunology, vol. 178, no. 10, pp. 6092–6099, 2007.
[11]
S. Tayebi and A. Mohamadkhani, “The TNF-alpha-308 promoter gene polymorphism and chronic HBV infection,” Hepatitis Research and Treatment, vol. 2012, Article ID 493219, 2012.
[12]
R. Avila-Flores and R. A. Medellín, “Ecological, taxonomic, and physiological correlates of cave use by Mexican bats,” Journal of Mammalogy, vol. 85, no. 4, pp. 675–687, 2004.
[13]
D. J. Decker, P.-J. Linton, S. Zaharevitz, M. Biery, T. R. Gingeras, and N. R. Klinman, “Defining subsets of naive and memory B cells based on the ability of their progeny to somatically mutate in vitro,” Immunity, vol. 2, no. 2, pp. 195–203, 1995.
[14]
M. S. Cragg, C. A. Walshe, A. O. Ivanov, and M. J. Glennie, “The biology of CD20 and its potential as a target for mAb therapy,” Current directions in autoimmunity, vol. 8, pp. 140–174, 2005.
[15]
K. Ishaka, A. Baptistab, L. Bianchic, F. Callead, J. D. Grootee, and F. Gudatf, “Histological grading and staging of chronic hepatitis,” Journal of Hepatology, vol. 22, pp. 696–699, 1995.
[16]
R. K. Bhogal and C. A. Bona, “B cells: no longer bystanders in liver fibrosis,” Journal of Clinical Investigation, vol. 115, no. 11, pp. 2962–2965, 2005.
[17]
A. Mohamadkhani, F. Bastani, M. Sotoudeh et al., “Influence of B cells in liver fibrosis associated with hepatitis B virus harboring basal core promoter mutations,” Journal of Medical Virology, vol. 84, pp. 1889–1896, 2012.
[18]
A. P. Holt, Z. Stamataki, and D. H. Adams, “Attenuated liver fibrosis in the absence of B cells,” Hepatology, vol. 43, no. 4, pp. 868–871, 2006.
[19]
T. I. Novobrantseva, G. R. Majeau, A. Amatucci et al., “Attenuated liver fibrosis in the absence of B cells,” Journal of Clinical Investigation, vol. 115, no. 11, pp. 3072–3082, 2005.
