Hepatitis C Virus and the Humoral Immune System

• Define the relationships between HCV infection, B cell phenotype, and B cell function [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  Define the relationships between HCV infection, B cell phenotype, and B cell function
  
  

The long-term goal of our research is to understand why immune complexes (ICs) are produced in patients infected with HCV, and whether these complexes affect virus interaction with target cells. We have found that many patients infected with HCV have an increased frequency of circulating B cells, but no evidence that the increased B cells are activated of proliferating. One possible mechanism for such an increase would be a change in levels of chemokines that influence B cell localization and trafficking. Our studies are aimed at testing the following hypotheses:

1. One hypothesis is that HCV infection results in increased levels of specific cytokines and chemokines that may affect the motility and localization of immature and mature B cells. An alternative model is that HCV infection leads to chronic antigenic stimulation of B lymphocytes, and that the abnormalities of B cell function associated with HCV infection reflect this chronic antigenic stimulation.
2. A second hypothesis is that autoantibodies and immune complexes present in HCV patient serum contribute to the persistence and spread of viral infection.

To test these hypotheses, we are measuring levels of chemokines, the frequency of circulating B cells (mature resting B cells, mature activated B cells, memory B cells, and immature B cells), and the levels and components of ICs in the blood of HCV-infected patients. Controls include healthy volunteers and patients with chronic liver disease unrelated to HCV infection. No interventions in patient care are planned. When patients elect to undergo standard antiviral therapies under the supervision of their hepatologists, we will study the outcomes of therapy (no virologic response, partial or transient virologic response, sustained virologic response) to determine whether any of the observed alterations in chemokine levels, B cell frequency or activation, or immune complex levels correlate with the patient's response to antiviral therapy.