TY - JOUR
T1 - Germinal centre-driven maturation of B cell response to mRNA vaccination
AU - Kim, Wooseob
AU - Zhou, Julian Q.
AU - Horvath, Stephen C.
AU - Schmitz, Aaron J.
AU - Sturtz, Alexandria J.
AU - Lei, Tingting
AU - Liu, Zhuoming
AU - Kalaidina, Elizaveta
AU - Thapa, Mahima
AU - Alsoussi, Wafaa B.
AU - Haile, Alem
AU - Klebert, Michael K.
AU - Suessen, Teresa
AU - Parra-Rodriguez, Luis
AU - Mudd, Philip A.
AU - Whelan, Sean P.J.
AU - Middleton, William D.
AU - Teefey, Sharlene A.
AU - Pusic, Iskra
AU - O’Halloran, Jane A.
AU - Presti, Rachel M.
AU - Turner, Jackson S.
AU - Ellebedy, Ali H.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/4/7
Y1 - 2022/4/7
N2 - Germinal centres (GC) are lymphoid structures in which B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells1–5 (BMPCs). 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 remain unknown. Here, we detected SARS-CoV-2 spike protein-specific MBCs in 42 individuals who had received two doses of the SARS-CoV-2 mRNA vaccine BNT162b2 six month earlier. Spike-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 B cells and plasma cells and BMPCs from eight individuals and expression of the corresponding monoclonal antibodies, we tracked the evolution of 1,540 spike-specific B cell clones. On average, early blood spike-specific plasmablasts exhibited the lowest SHM frequencies. By contrast, SHM frequencies of spike-specific GC B cells increased by 3.5-fold within six months after vaccination. Spike-specific MBCs and BMPCs accumulated high levels of SHM, which corresponded with enhanced anti-spike antibody avidity in blood and enhanced affinity as well as neutralization capacity of BMPC-derived monoclonal antibodies. We report how the notable persistence of the GC reaction induced by SARS-CoV-2 mRNA vaccination in humans culminates in affinity-matured long-term antibody responses that potently neutralize the virus.
AB - Germinal centres (GC) are lymphoid structures in which B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells1–5 (BMPCs). 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 remain unknown. Here, we detected SARS-CoV-2 spike protein-specific MBCs in 42 individuals who had received two doses of the SARS-CoV-2 mRNA vaccine BNT162b2 six month earlier. Spike-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 B cells and plasma cells and BMPCs from eight individuals and expression of the corresponding monoclonal antibodies, we tracked the evolution of 1,540 spike-specific B cell clones. On average, early blood spike-specific plasmablasts exhibited the lowest SHM frequencies. By contrast, SHM frequencies of spike-specific GC B cells increased by 3.5-fold within six months after vaccination. Spike-specific MBCs and BMPCs accumulated high levels of SHM, which corresponded with enhanced anti-spike antibody avidity in blood and enhanced affinity as well as neutralization capacity of BMPC-derived monoclonal antibodies. We report how the notable persistence of the GC reaction induced by SARS-CoV-2 mRNA vaccination in humans culminates in affinity-matured long-term antibody responses that potently neutralize the virus.
UR - http://www.scopus.com/inward/record.url?scp=85127418875&partnerID=8YFLogxK
U2 - 10.1038/s41586-022-04527-1
DO - 10.1038/s41586-022-04527-1
M3 - Article
C2 - 35168246
AN - SCOPUS:85127418875
SN - 0028-0836
VL - 604
SP - 141
EP - 145
JO - Nature
JF - Nature
IS - 7904
ER -