B cell homeostasis in chronic hepatitis C virus-related mixed cryoglobulinemia is maintained through naïve B cell apoptosis.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Lauren E HolzBarbara Rehermann

Abstract

Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of chronic hepatitis C virus (HCV) infection. Although the formation of inflammation-triggering immune complexes is driven by clonal expansions of autoreactive B cells, we found total B cell numbers paradoxically reduced in HCV-infected patients with MC. HCV patients with MC (n = 17) also displayed a reduced number and a reduced frequency of naïve B cells compared with HCV-infected patients without MC (n = 19), hepatitis B virus-infected patients (n = 10), and uninfected controls (n = 50). This was due to an increased sensitivity of naïve B cells to apoptosis resulting in a reduction in the size of the naïve B cell subset. In addition, 4-fold expansion and skewing (lower T1/T2-ratio) of the immature B cell subset was noted in MC patients, suggesting that apoptosis of naïve B cells triggered the release of B cell precursors from bone marrow in an attempt to maintain normal B cell numbers. Following treatment of MC with the B cell-depleting antibody rituximab, the size of all B cell subsets, the T1/T2-ratio, and the cyroglobulin levels all normalized. Cryoglobulin levels correlated with in vivo proliferation of T2 B cells, suggesting a link between the skew...Continue Reading

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Nov 28, 2012·Current HIV/AIDS Reports·Rebecca R Terilli, Andrea L Cox
Sep 7, 2012·Clinical & Developmental Immunology·Valli De ReOmbretta Repetto
Nov 18, 2014·Rheumatic Diseases Clinics of North America·Daniela GhetieCailin H Sibley
Jun 8, 2013·The American Journal of the Medical Sciences·Hao WuXiang Li
Sep 13, 2015·Best Practice & Research. Clinical Rheumatology·Gim Gee Teng, W Winn Chatham
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Nov 18, 2015·World Journal of Gastroenterology : WJG·Faezeh GhasemiZahra Meshkat
Aug 16, 2017·Experimental and Therapeutic Medicine·Fanyun KongLai Wei
Mar 19, 2020·Journal of Translational Medicine·Yang ZhouTao Jin

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis