Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C

Intrahepatic lymphoid follicle (ILF) formation is one of the most character istic and commonly observed histological features in patients with chronic hepatitis C. However, little is known regarding whether follicles in the li ver belong to functional lymphoid tissues, where B cells are activated, dif ferentiated, and proliferated, or if the lymphocytes are merely infiltrated after recruitment from the secondary lymphoid organs. To ascertain this po ssibility, we examined the expression of markers for B-cell activation, dif ferentiation, and proliferation in ILFs in patients with chronic hepatitis C using surgically resected specimens, and compared them with specimens of perihepatic lymph nodes by an immunohistochemical technique. Germinal cente r (GC) formation in the ILFs was frequently found in HCV-positive cases. Th e distribution of immunoglobulin M (IgM)-, IgD-, and IgG-positive cells and the expression patterns of Ki-67, CD23, or bcl-2 and bcl-6 gene products i n the follicles with GC formation in the liver of patients with chronic hep atitis C were similar to those of lymph nodes, indicating that B cells are activated, proliferated, and differentiated in the ILFs with GC formation i n patients with chronic hepatitis C. Oligoclonal expansion of B cells in th e livers with ILFs was confirmed by an analysis of immunoglobulin heavy cha in (IgH) gene rearrangement determined by polymerase chain reaction (PCR). These data strongly suggest that ILFs with GC formation, which are frequent ly found in patients with chronic hepatitis C, may functionally be the same as those found in lymph nodes with respect to B-cell expansion and maturat ion.