ADAPTIVE NK CELLS ACQUIRE B-LYMPHOCYTE CD19 SURFACE MARKER VIA TROGOCYTOSIS DURING ACTIVATION OF CHRONIC EBV INFECTION



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Abstract

Abstract

In the last decade, there have been reports of NK with low CD19 coexpression in the blood and bone marrow. There is no data on their association with pathology. We have previously shown that CD19+dim NK has an adaptive phenotype. A possible reason for the appearance of CD19 on NK may occur via trogocytosis of B-lymphocytes during active EBV infection.

The aim of study is to identify factors contributing to the appearance of a CD56+CD19+dim NK in the peripheral blood of patients with herpes infection.

Materials and methods.  Blood, saliva, and other biological fluids from 225 patients (34.6±8.5 years, 71% women) were analyzed. Chronic persistent EBV infection was noted in 29%, CMV – in 2.2%, mixed infection – in 10%. IgM to CMV and IgG with avidity were determined in serum; CMV and EBV DNA in biological fluids. Subpopulations of blood lymphocytes were studied by flow cytometry to quantitate CD19+dim NK cell level.

In individuals without IgG to CMV, CD19+dim NK were not determined. A relationship was found between the presence of DNA of each virus and the presence of CD19+dim NK cells. The proportion of CD19+dim NK cells peaked at active replication of both viruses and decreased in the absence of CMV replication. Among individuals with mixed infection, cell subpopulation was identified in the group of younger patients with long-term chronic EBV infection. In this group, no significant changes in the content of total immunoglobulins were detected; no diseases in history that suppress an adequate humoral immunity were observed. Among individuals with mixed infection, but without CD19+dim NK cells, a decrease in total immunoglobulins and the presence of diseases leading to altered production of specific immunoglobulins were more often noted.

The appearance of CD19+dim NK cells in the blood is facilitated by CMV infection, the presence of long-term chronic EBV infection with activation at the time of the study, and an intact humoral immunity. CD19+dim NK cells are not detected in individuals without IgG to CMV, in the absence of EBV activation, in the presence of diseases that lead to impaired humoral immunity. The appearance of the CD56+CD19+dim NK cells in the blood is a consequence of the participation of adaptive NK cells in the antiviral response with a high level of neutralizing antibodies and a marker of trogocytosis of B-cells that have bound EBV. The possibility of the presence of CD19+dim NK cells in the blood must be taken into account when phenotyping B-cells.

About the authors

Anastasia Andreevna Kalashnikova

The Nikiforov Russian Centre of Emergency and Radiation Medicine EMERCOM of Russia, Saint Petersburg, Russia

Email: petkova_nas@mail.ru
ORCID iD: 0000-0002-5338-0866
SPIN-code: 1774-9995
Scopus Author ID: 6602731034
ResearcherId: MBH-9003-2025

PhD (Biology), Senior Researcher, Research Department of Laboratory Diagnostics

Россия, St. Petersburg, st. Optikov, 54

Nataliya Vladimirovna Bychkova

National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov, Moscow, Russia

Email: bnv19692007@yandex.ru
ORCID iD: 0000-0002-6907-2817
SPIN-code: 6873-4944

Doctor of Biology, Leading Researcher, Laboratory of Clinical Immunology

Россия, Moscow, st. Academician Oparina, 4

Irina Anisimovna Rakityanskaya

Department of Allergology, Immunology and Clinical Transfusiology, Municipal Outpatient Hospital no. 112, Saint Petersburg, Russia

Author for correspondence.
Email: tat-akyla@inbox.ru
ORCID iD: 0000-0003-2524-4602
SPIN-code: 5777-2740
Scopus Author ID: 6505921346

MD, Clinical Immunologist; Professor, consultant immunologist Outpatient Unit of Allergology, Immunology, and Clinical Transfusiology.

Россия, St. Petersburg, st. Academician Baykova, 25, bldg. 1

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