Related Experiment Videos
Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C
J Murakami1, Y Shimizu, Y Kashii
1Third Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
Insights
Intrahepatic lymphoid follicles (ILFs) in chronic hepatitis C patients form germinal centers, indicating B cells activate, proliferate, and differentiate within the liver. These findings suggest ILFs function similarly to lymph nodes in B-cell maturation.
Area of Science:
- Immunology
- Hepatology
- Pathology
Background:
- Intrahepatic lymphoid follicles (ILFs) are common in chronic hepatitis C.
- The functional role of ILFs in B-cell activity remains unclear.
- It's debated whether ILFs are functional lymphoid tissues or sites of lymphocyte infiltration.
Purpose of the Study:
- To investigate if ILFs in chronic hepatitis C patients are functional lymphoid tissues.
- To examine B-cell activation, differentiation, and proliferation within ILFs.
- To compare ILF characteristics with those of perihepatic lymph nodes.
Main Methods:
- Immunohistochemical analysis of surgically resected liver specimens.
- Examination of B-cell activation and differentiation markers (IgM, IgD, IgG, Ki-67, CD23, bcl-2, bcl-6).
- Analysis of immunoglobulin heavy chain (IgH) gene rearrangement via PCR to confirm B-cell expansion.
Main Results:
- Germinal center (GC) formation was frequently observed in ILFs of HCV-positive cases.
- B-cell marker distribution and proliferation markers in ILFs mirrored those in lymph nodes.
- Oligoclonal expansion of B cells in the liver was confirmed by IgH gene rearrangement analysis.
Conclusions:
- ILFs with GC formation in chronic hepatitis C patients exhibit B-cell activation, proliferation, and differentiation.
- These ILFs appear to function similarly to lymph node germinal centers.
- The liver, in the context of chronic hepatitis C, can host functional lymphoid tissue.
Abstract:
Intrahepatic lymphoid follicle (ILF) formation is one of the most characteristic and commonly observed histological features in patients with chronic hepatitis C. However, little is known regarding whether follicles in the liver belong to functional lymphoid tissues, where B cells are activated, differentiated, and proliferated, or if the lymphocytes are merely infiltrated after recruitment from the secondary lymphoid organs. To ascertain this possibility, we examined the expression of markers for B-cell activation, differentiation, 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 center (GC) formation in the ILFs was frequently found in HCV-positive cases. The 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 in the follicles with GC formation in the liver of patients with chronic hepatitis C were similar to those of lymph nodes, indicating that B cells are activated, proliferated, and differentiated in the ILFs with GC formation in patients with chronic hepatitis C. Oligoclonal expansion of B cells in the livers with ILFs was confirmed by an analysis of immunoglobulin heavy chain (IgH) gene rearrangement determined by polymerase chain reaction (PCR). These data strongly suggest that ILFs with GC formation, which are frequently 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 maturation.