Tfh cells and the germinal center are required for memory B cell formation & humoral immunity after ChAdOx1 nCoV-19 vaccination

• Published in: Cell reports. Medicine Vol. 3; no. 12; p. 100845
• Main Authors: Foster, William S., Lee, Jia Le, Thakur, Nazia, Newman, Joseph, Spencer, Alexandra J., Davies, Sophie, Woods, Danielle, Godfrey, Leila, Hay, Iain M., Innocentin, Silvia, Yam-Puc, Juan Carlos, Horner, Emily C., Sharpe, Hayley J., Thaventhiran, James E., Bailey, Dalan, Lambe, Teresa, Linterman, Michelle A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.12.2022
• Subjects: CD40L; ChAdOx1 nCoV-19; COVID-19 - prevention & control; Germinal Center; Humans; Immunity, Humoral; Immunization, Secondary; Memory B Cells; SARS-CoV-2; T Follicular Helper Cells; T-Lymphocytes, Helper-Inducer; Tfh cells; Vaccination; vaccine; CD40L; vaccine; SARS-CoV-2; germinal center; ChAdOx1 nCoV-19; Tfh cells
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2022.100845

Emergence from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been facilitated by the rollout of effective vaccines. Successful vaccines generate high-affinity plasma blasts and long-lived protective memory B cells. Here, we show a requirement for T follicular helper (Tfh) cells and the germinal center reaction for optimal serum antibody and memory B cell formation after ChAdOx1 nCoV-19 vaccination. We found that Tfh cells play an important role in expanding antigen-specific B cells while identifying Tfh-cell-dependent and -independent memory B cell subsets. Upon secondary vaccination, germinal center B cells generated during primary immunizations can be recalled as germinal center B cells again. Likewise, primary immunization GC-Tfh cells can be recalled as either Tfh or Th1 cells, highlighting the pluripotent nature of Tfh cell memory. This study demonstrates that ChAdOx1 nCoV-19-induced germinal centers are a critical source of humoral immunity. [Display omitted] •Tfh cells are required for RBD+ B cell selection after ChAdOx1 nCoV-19 vaccination•Absence of GC B cells limits RBD+ B cell expansion and serum immunity•RBD+ B cells are recalled to the GC during secondary responses•GC Tfh cells are recalled during secondary responses as Tfh cells or as Th1 cells Effective vaccines elicit protective humoral immunity. Foster et al. use high-parameter flow cytometry and confocal microscopy to demonstrate that vaccine-induced germinal centers are a critical source of humoral immunity following ChAdOx1 nCoV-19 vaccination.