B CELLS AND FOLLICULAR T-HELPER CELLS IN PATIENTS WITH LUNG TUBERCULOSIS



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Abstract

M.tuberculosis-related mortality and morbidity remain one of the most relevant public health issues. Cell-mediated reactions involving both innate and adaptive cells play a major role protecting against M.tuberculosis. However, but it was noticed recently that diverse B cell subsets are also critical for controlling M.tuberculosis infection. Hence, our study was aimed to assess patterns for B cell subsets and circulating memory follicular Th (Tfh) cell subsets in patients with pulmonary tuberculosis (TB). Peripheral blood samples were collected from treatment naïve TB patients (TB, n=37), and age- and gender-matched healthy controls (HC, n=39). Lymphocytes were stained with fluorochrome-labeled antibodies to define B cell and Tfh cell subsets using multicolor flow cytometry. It was found that the percentage of IgD+CD27–СD38– ‘naïve’ B cells was increased, whereas that of for IgD+CD27–CD38+ activated ‘naive’ and IgD+CD27–CD38++ circulating germinal-center B cell precursors decreased in TB patients vs. control. The decreased relative and absolute frequencies of IgD+CD27+ unswitched memory B cells, as well as the decreased relative numbers of IgD–CD27+ switched memory B cells were found in TB patients vs. control. We revealed the increased relative and absolute numbers of CD24+++CD38+++ Breg cells in TB group vs. control (7,83% (5,61; 15,14) vs. 4,84% (2,38; 7,15), and 15 cell/1μL (10; 26) vs. 9 cell/1μL (4; 17), р=0,001 and р=0,010, respectively). TB patients vs. control had decreased relative and absolute frequencies of CXCR3+CCR6– Tfh1 cells (27,86% (22,36; 32,04) vs. 32,27% (26,02; 36,65), р=0,009, and 26 cell/1μL (14; 45) vs. 37 cell/1μL (26; 48), р=0,011). Furthermore, the frequencies of circulating Tfh1 cells negatively correlated with the frequencies of IgD+CD27–CD38++ B cells (r=0,425, р=0,017) and CD24+++CD38+++ Bregs (r=0,569, р=0,001). Finally, we noticed that in patients with TB vs. control subjects CXCR3–CCR6– Tfh2 level was increased (20,55% (15,84; 26,20) vs. 16,86% (14,39; 22,05), p=0,022), and correlated with the relative frequency of IgD+CD27–CD38+ ‘naïve’ В cells (r=0,415, р=0,020). Thus, the data obtained allow to presume that peripheral blood B cell and Tfh cell subset compositions in pulmonary TB patients are disturbed suggesting that humoral immune response may be altered not only locally (in the site of infection), but also at the level of peripheral lymphoid tissues.

About the authors

Igor V. Kudryavtsev

Institute of Experimental Medicine, St.Petersburg, Russian Federation

Email: igorek1981@yandex.ru

PhD (Biology), Head of laboratory of cellular immunology; Assistant Professor, Department of Immunology, 

Russian Federation

Artem A. Rubinstein

Institute of Experimental Medicine, St.Petersburg, Russian Federation

Email: arrubin6@mail.ru

Junior Researcher, Cell Immunology Laboratory, Department of Immunology

Russian Federation, 197376, St. Petersburg, acad. Pavlov str., 12, Scientific Research Institute of Experimental Medicine

Anna A. Starshinova

Almazov National Medical Research Centre, St.Petersburg, Russian Federation;
St. Petersburg State University, St. Petersburg, Russian Federation

Email: starshinova_777@mail.ru

PhD, MD (Medicine), Leading Researcher of the Laboratory of Probabilistic Methods in Analysis, Faculty of Mathematics and Computer Science, Saint Petersburg State University; Head of the Research Department, Professor of the Department of Faculty Therapy with a Clinic, Almazov National Medical Research Center of the Ministry of Health of the Russian Federation, 2 Akkuratova St., Saint Petersburg

Russian Federation

Adilya R. Sabirova

St. Petersburg State University, St. Petersburg, Russian Federation;
Bashkir State Medical University, Ufa, Russian Federation

Email: starshinova_777@mail.ru

Junior Researcher, Laboratory of Probabilistic Methods in Analysis, Faculty of Mathematics and Computer Science, St. Petersburg State University; Assistant, Department of Phthisiology, Bashkir State Medical University

Russian Federation

Ekaterina Nikolaevna Belyaeva Nikolaevna

St. Petersburg State University, St. Petersburg, Russian Federation

Email: igorek1981@yandex.ru

MD, PhD, Senior Researcher, Laboratory of Probabilistic Methods in Analysis, Faculty of Mathematics and Computer Science, St. Petersburg State University, Chief Physician of the Republican Anti-Tuberculosis Dispensary, Petrozavodsk, Russia 

Russian Federation

Dmitry A. Kudlai

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation;
NRC Institute of Immunology FMBA of Russia, Moscow, Russian Federation;
Lomonosov Moscow State University, Moscow, Russian Federation

Author for correspondence.
Email: D624254@gmail.com
ORCID iD: 0000-0003-1878-4467
SPIN-code: 4129-7880
Scopus Author ID: 921055

corresponding member of the Russian Academy of Sciences, DMedSci, MD, Professor of the Department of Pharmacology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation; Professor of the Department of Pharmacognosy and Industrial Pharmacy, Faculty of Fundamental Medicine, Lomonosov Moscow State University. Leading Researcher, Laboratory of Personalized Medicine and Molecular Immunology, NRC Institute of Immunology FMBA of Russia

Russian Federation, Moscow; Moscow

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