PERIPHERAL BLOOD B‑CELL SUBPOPULATIONS IN CHRONIC HEPATITIS B AND C VIRUS INFECTIONS



Cite item

Full Text

Abstract

Chronic infections caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) remain a significant public health concern. Although T‑cell exhaustion plays a key role in the immunity behind the disease, B lymphocytes function and distribution in these infections remain poorly understood. The aim of this study was to compare the distribution of major and minor peripheral B‑cell subsets in patients with chronic hepatitis C (CHC) and chronic hepatitis B (CHB). The study included 39 patients with CHC, 28 patients with CHB, and 30 healthy donors. The B‑cell (CD19⁺) subpopulation composition was evaluated with flow cytometry based on the expression of CD5, CD27, and CD38. Statistical analysis was performed with nonparametric tests. The total number of CD19⁺ B cells did not differ between the groups. However, in both patient cohorts, we observed a significant decrease in the relative and absolute proportions of B1 cells (CD5+) compared to the healthy donors (p < 0.0001 for both), accompanied by a compensatory increase in B2 cells (CD5-). The share of mature activated B cells (CD27+CD38+) was lower in both CHC and CHB patients (p = 0.0142 and p = 0.0014, respectively). Plasmablast counts (CD27++CD38++) decreased in both groups, with the most pronounced reduction observed in CHB patients (p < 0.0001 vs. controls). Transitional B cells (CD27-CD38++) significantly decreased in CHB patients, both in relative and absolute values (p < 0.0001 vs. CHC, p = 0.0134 vs. controls). No statistically significant changes were found in the proportions of mature naive cells, memory cells, or double‑negative (DN) cells. Chronic HBV and HCV infections are associated not with a quantitative B‑cell deficiency but with a subpopulation redistribution, demonstrated by a reduction in B1 cells, mature activated B cells, and plasmablasts. A specific hallmark of CHB is the decrease in transitional B cells, which may indicate impairments in the early stages of B‑cell maturation. Our findings highlight the importance of analyzing minor cell subsets for a better understanding of pathological processes behind of chronic viral hepatitis.

About the authors

Anastasia Alexandrovna Butenko

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Email: aabutenko15@gmail.com

Laboratory research assistant, Laboratory of Molecular Immunology

Russian Federation, St. Petersburg

Natalia Alexandrovna Arsentieva

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation

Email: arsentieva_n.a@bk.ru
ORCID iD: 0000-0003-2490-308X

PhD Biology, Senior Reseacher, Laboratory of Molecular Immunology

associate professor of department of Immunology

Russian Federation, St. Petersburg St. Petersburg

Zoya Romanovna Korobova

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation

Email: zoia-korobova@yandex.ru
ORCID iD: 0000-0003-0535-5014

Researcher, Laboratory of Molecular Immunology

assistant professor of department of Immunology 

Russian Federation, St. Petersburg; St. Petersburg

Sergey Alexandrovich Maslov

S. M. Kirov Military Medical Academy, St. Petersburg, Russian Federation

Email: maslovsergal@mail.ru

Head of the clinic department of the Department of Infectious Diseases (with a course in medical parasitology and tropical diseases)

Russian Federation, St. Petersburg

Konstantin Vadimovich Kozlov

S. M. Kirov Military Medical Academy, St. Petersburg, Russian Federation

Email: kosttiak@mail.ru

Doctor of Medical Sciences, Professor, Head of the Department of Infectious Diseases (with a course in medical parasitology and tropical diseases)

St. Petersburg

Dmitrii Leonidovich Sulima

EXCLUSIVE Medical Clinic, St. Petersburg, Russian Federation

Email: uncledimamed@mail.ru
ORCID iD: 0000-0002-3735-5783

Doctor of Medical Sciences, Head of the Innovative Hepatology Department

Russian Federation, St. Petersburg

Oksan Yurievna Rishnyak

Vsevolozhsk Clinical Hospital, Leningrad region, Russian Federation

Email: infekt@mail.ru
ORCID iD: 0000-0002-3787-927X

Infectious disease specialist

Russian Federation, Leningrad region

Areg Artemovich Totolian

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation

Author for correspondence.
Email: totolian@spbraaci.ru
ORCID iD: 0000-0003-4571-8799
Scopus Author ID: 36884232100

MD, PhD, professor, Academician of Russian Academy of Science

a head of Saint Petersburg Pasteur Institute

chair of Department of Immunology 

Russian Federation, St. Petersburg St. Petersburg

References

  1. О состоянии санитарно-эпидемиологического благополучия населения в Российской Федерации в 2025 году: Государственный доклад. Москва: Федеральная служба по надзору в сфере защиты прав потребителей и благополучия человека, 2026. – 407 с.
  2. State Report on the Sanitary and Epidemiological Well‑Being of the Population in the Russian Federation for 2025. Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Well‑being, 2026. 407 p. https://36.rospotrebnadzor.ru/download/gdrf/gdrf2025.pdf
  4. Arsentieva N.A., Elezov D.S., Kudryavtsev I.V., Korobova Z.R., Totolian A.A. Peripheral blood B-cells and CXCR3 expression in chronic hepatitis C virus infection. Russian Journal of Infection and Immunity, 2025, Vol. 15, no. 3, pp. 529–535.
  5. doi: 10.15789/2220-7619-PBB17939
  6. Cascino K., Liechti T., Seaberg E.C., Stevens K.E., Wolinsky S.M., Witt M.D., Mailliard R.B., Roederer M., Bailey J.R., Thio C.L., Cox A.L.
  7. HIV causes global B cell dysregulation and restricts HBV-specific B cell development in an incident HBV cohort. J Clin Invest., 2026, Vol. 136, no. 11, :e203138.
  8. doi: 10.1172/JCI203138.
  9. Enyindah-Asonye G., Nwankwo A., Hogge C., Rahman M.A., Helmold Hait S., Hunegnaw R., Ko E.-J., Hoang T., Venzon D.J. and Robert-Guroff M. A Pathogenic Role for Splenic B1 Cells in SIV Disease Progression in Rhesus Macaques. Front. Immunol., 2019, 10:511. doi: 10.3389/fimmu.2019.00511
  10. Esser K., Cheng X., Wettengel J.M., Lucifora J., Hansen-Palmus L., Austen K., Roca Suarez A.A., Heintz S., Testoni B., Nebioglu F., Pham M.T., Yang S., Zernecke A., Wohlleber D., Ringelhan M., Broxtermann M., Hartmann D., Hüser N., Mergner J., Pichlmair A., Thasler W.E., Heikenwalder M., Gasteiger G., Blutke A., Walch A., Knolle P.A., Bartenschlager R., Protzer U. Hepatitis B Virus Targets Lipid Transport Pathways to Infect Hepatocytes. Cell Mol Gastroenterol Hepatol., 2023, Vol. 16, no. 2, pp. 201-221. doi: 10.1016/j.jcmgh.2023.03.011.
  11. Ishikawa S., Matsushima K. Aberrant B1 cell trafficking in a murine model for lupus. Front Biosci., 2007, Vol. 12, pp. 1790-803.
  12. doi: 10.2741/2188
  13. Korobova Z.R., Arsentieva N.A., Butenko A.A., Batsunov O.K., Lyubimova N.E., Ostankova Y.V., Anufrieva E.V., Maslov S.A., Kozlov K.V., Sulima D.L., Rishnyak O.Y., Totolian A.A. Disease-Associated Shifts in Minor T Cell Subpopulations Define Distinct Immunopathology in HBV vs. HCV Infection. Int J Mol Sci., 2025, Vol. 26, no. 16:7761. doi: 10.3390/ijms26167761.
  14. Kumar A., Hossain R.A., Yost S.A., Bu W., Wang Y., Dearborn A.D., Grakoui A., Cohen J.I., Marcotrigiano J. Structural insights into hepatitis C virus receptor binding and entry. Nature, 2021, Vol. 598, pp. 521–525. doi: 10.1038/s41586-021-03913-5.
  15. Nishio A., Hasan S., Park H., Park N., Salas J.H., Salinas E., Kardava L., Juneau P., Frumento N., Massaccesi G., Moir S., Bailey J.R., Grakoui A., Ghany M.G., Rehermann B. Serum neutralization activity declines but memory B cells persist after cure of chronic hepatitis C. Nat Commun, 2022, Vol. 13, 5446. doi: 10.1038/s41467-022-33035-z
  16. Oliviero B., Cerino A., Varchetta S., Paudice E., Pai S., Ludovisi S., Zaramella M., Michelone G., Pugnale P., Negro F., Barnaba V., Mondelli M.U. Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections. J Hepatol., 2011, Vol. 55, no. 1, pp. 53-60. doi: 10.1016/j.jhep.2010.10.016.
  17. Osmani Z., Boonstra A. Recent Insights into the Role of B Cells in Chronic Hepatitis B and C Infections. Pathogens, 2023, Vol. 12, 815. doi: 10.3390/pathogens12060815
  18. Rouers A., Appanna R., Chevrier M., Lum J., Lau M.C., Tan L., Loy T., Tay A., Sethi R., Sathiakumar D., Kaur K., Böhme J., Leo Y.S., Renia L., Howland S.W., Singhal A., Chen J., Fink K.. CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function. iScience, 2021, Vol. 24, no. 5, 102482. doi: 10.1016/j.isci.2021.102482.
  19. Shoukry N.H., Walker C.M. T cell responses during HBV and HCV infections: similar but not quite the same? Current Opinion in Virology, 2011, Vol. 51, pp. 80-86. doi: 10.1016/j.coviro.2021.08.011.
  20. Zhou Y., Zhang Y., Han J., Yang M., Zhu J., Jin T. Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases. J Transl Med., 2020, Vol. 18, no. 1, 131. doi: 10.1186/s12967-020-02289-w.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) Butenko A.A., Arsentieva N.A., Korobova Z.R., Maslov S.A., Kozlov K.V., Sulima D.L., Rishnyak O.Y., Totolian A.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № 77 - 11525 от 04.01.2002.