김우섭 (Washington University School of Medicine in St. Louis)

한빛사논문

조회2,471

Washington University School of Medicine in St. Louis

Nature, Published: 15 February 2022 | https://doi.org/10.1038/s41586-022-04527-1 Germinal centre-driven maturation of B cell response to mRNA vaccination

Wooseob Kim^1,11, Julian Q. Zhou^1,11, Stephen C. Horvath¹, Aaron J. Schmitz¹, Alexandria J. Sturtz¹, Tingting Lei¹, Zhuoming Liu², Elizaveta Kalaidina³, Mahima Thapa¹, Wafaa B. Alsoussi¹, Alem Haile⁴, Michael K. Klebert⁴, Teresa Suessen⁵, Luis Parra-Rodriguez⁶, Philip A. Mudd^7,8, Sean P. J. Whelan², William D. Middleton⁵, Sharlene A. Teefey⁵, Iskra Pusic⁹, Jane A. O’Halloran⁶, Rachel M. Presti^6,8, Jackson S. Turner¹ & Ali H. Ellebedy^1,8,10,*

¹Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. ²Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. ³Division of Allergy and Immunology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. ⁴Clinical Trials Unit, Washington University School of Medicine, St. Louis, MO, USA. ⁵Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA. ⁶Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. ⁷Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA. ⁸Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA. ⁹Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. ¹⁰The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. ¹¹These authors contributed equally: Wooseob Kim, Julian Q. Zhou.

^*Corresponding author

Abstract

Germinal centres (GC) are lymphoid structures where B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells (BMPCs)1–5. SARS-CoV-2 mRNA vaccination induces a persistent GC response that lasts for at least six months in humans6–8. The fate of responding GC B cells as well as the functional consequences of such persistence have not been elucidated. We detected SARS-CoV-2 spike (S)-specific MBCs in 42 individuals who had received two doses of BNT162b2, a SARS-CoV-2 mRNA vaccine six months earlier. S-specific IgG-secreting BMPCs were detected in 9 out of 11 participants. Using a combined approach of sequencing the B cell receptors of responding blood plasmablasts and MBCs, lymph node GC and plasma cells and BMPCs from eight individuals and expression of the corresponding monoclonal antibodies (mAbs), we tracked the evolution of 1540 S-specific B cell clones. We show that early blood S-specific plasmablasts - on average - exhibited the lowest SHM frequencies. In comparison, SHM frequencies of S-specific GC B cells increased by 3.5-fold within six months after vaccination. S-specific MBCs and BMPCs accumulated high levels of SHM, which corresponded with enhanced anti-S antibody avidity in blood and affinity as well as neutralization capacity of BMPC-derived mAbs. This study documents how the striking persistence of SARS-CoV-2 vaccination-induced GC reaction in humans culminates in affinity-matured long-term antibody responses that potently neutralize the virus.

논문정보

형식Research article
게재일2022년 02월 (BRIC 등록일 2022-02-17)
연구진국외 연구진
분야 의약학 > 면역의학

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