Reversion of anergy signatures in clonal CD21low B cells of mixed cryoglobulinemia after clearance of HCV viremia.

Blood
Martina Del PadreMarcella Visentini

Abstract

Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM+CD27+ B cells. These cells display both the features of anergy induced by continual engagement of the B-cell receptor (BCR), such as high expression of phosphorylated extracellular signal-regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion, such as CD21low phenotype and a defective response to ligation of BCR and Toll-like receptor 9 (TLR9). MC usually regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect. We investigated the phenotypic and functional changes in clonal B cells of MC patients with sustained virologic responses to direct-acting antivirals (DAAs), which lack immunomodulatory properties. We found that high pERK expression and accelerated apoptosis revert within 4 weeks after beginning therapy, whereas clonal B cells unresponsive to TLR9 stimulation persist for at least 24 weeks, although they may partially rescue normal CD21 expression. Thus, similar to mouse models, features of anergy in MC B cells rapidly revert after disengagement from HCV, whereas virus-specific exhaustion imparts a durable inhibitory imprint on cell function. Trea...Continue Reading

References

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Citations

Jan 29, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Marcella VisentiniMilvia Casato
May 16, 2019·Current Opinion in Rheumatology·Dario RoccatelloSavino Sciascia
Aug 2, 2020·Digestive Diseases and Sciences·Ming-Ling ChangRong-Nan Chien
Jul 8, 2017·Blood·David E Kaplan
Oct 17, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Stefania ColantuonoMilvia Casato
Jun 24, 2019·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Y-T ChengM-L Chang

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