The "complexing" nature of B cells in hepatitis C virus infection: apoptosis versus survival

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIDDK	INFECTDIS-4

Authors

• L Holz
• JC Yoon
• S Raghuraman
• S Moir
• M Sneller
• B Rehermann

Abstract

Cryoglobulinemia remains the most common extrahepatic manifestation, of chronic hepatitis C virus (HCV) infection, and is characterized by the presence of immune complexes in the blood that can trigger life-threatening conditions. Clonal expansions of autoreactive memory B cells drive the formation of these immune complexes but HCV patients with cryoglobulinemia (HCV+MC) have normal B cell numbers. To investigate this phenomenon, we performed a cross-sectional study investigating B cell subsets in HCV patients, HCV+MC patients and healthy controls. HCV+MC patients displayed 4-fold expansions of activated and immature B cells, a shift from immature transitional T1 to T2 B cells, and reductions in naïve B cells. The increased size of the immature B cell subset in HCV patients was found to be secondary to increased naïve B cell apoptosis. In addition we studied the effects of Rituximab, a B cell depleting antibody, in HCV+MC patients. We found that newly generated B cells were more akin to B cells in healthy individuals as evidenced by a normal T1/T2 ratio and reduced percentages of activated B cells. This study provides new insight into the complexity of B cell homeostasis in chronic HCV patients with cryoglobulinemia and explains the mechanism of action of Rituximab.

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