CD20<SUP>+</SUP> natural killer cells are polyfunctional, memory-like cells that are enriched in inflammatory disorders
Creators
- Albayrak, Ozgur1
- Tiryaki, Ergun2
- Akkaya, Nazan2
- Kizilirmak, Ali Burak2
- Doran, Tansu2
- Gokmenoglu, Gokce2
- Yuksel, Muhammed1
- Ulukan, Burge2
- Uzulmez, Mina3
- Baytekin, Isil3
- Soylu, Onder Kemal3
- Esendagli, Gunes4
- Meinl, Ingrid5
- Koseoglu, Mesrure3
- Yuksel, Burcu3
- Erus, Suat6
- Arikan, Cigdem
- Vural, Secil
- Zeybel, Mujdat
- Soysal, Aysun3
- 1. Koc Univ, Res Ctr Translat Med, Istanbul, Turkiye
- 2. Koc Univ, Grad Sch Hlth Sci, Istanbul, Turkiye
- 3. Bakirkoy Prof Dr Mazhar Osman Educ & Res Hosp Psyc, Neurol Dept, Istanbul, Turkiye
- 4. Hacettepe Univ, Canc Inst, Dept Basic Oncol, Ankara, Turkiye
- 5. Ludwig Maximilians Univ Munchen, Univ Hosp, Inst Clin Neuroimmunol, Munich, Germany
- 6. Koc Univ, Sch Med, Dept Thorac Surg, Istanbul, Turkiye
Description
While CD20 was initially characterized as a B cell-specific marker, its expression on memory T cells has expanded our understanding of this molecule's distribution and function. Here, we identify a previously unrecognized CD20-expressing NK cell population and demonstrate its functional significance. CD56(+)CD20(+) NK cells exhibit hallmarks of cellular activation, including elevated NKp46, CD69, and CD137 expression, enhanced proliferative capacity, and increased production of inflammatory cytokines (IFN-gamma, GM-CSF, TNF-alpha, IL-10). Functional analyses revealed enhanced cytotoxicity against K562 targets, correlating with increased expression of cytolytic mediators including granzymes A, B, and K, perforin, FASL, and TRAIL. Single-cell transcriptional profiling demonstrated that MS4A1-expressing NK cells possess a distinct molecular signature characterized by elevated granzyme K expression and memory-like features. These cells preferentially localize to secondary lymphoid organs and accumulate in inflammatory tissues. Notably, CD56(+)CD20(+) NK cells are enriched in multiple inflammatory conditions, including multiple sclerosis, autoimmune hepatitis, hepatitis B infection, hepatocellular carcinoma, and lung cancer. Treatment with rituximab depletes this population, suggesting potential therapeutic implications. Our findings establish CD20(+) NK cells as a functionally distinct lymphocyte subset with enhanced effector capabilities and tissue-homing properties, providing new insights into immune regulation in inflammatory diseases.
Files
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