tetano
Editor, Senior Moderator
Eur J Immunol
. 2026 Jan;56(1):e70127.
doi: 10.1002/eji.70127. SARS-CoV-2 mRNA Vaccination Leads to Transient Humoral and B Cell Bystander Responses in Adults
Lisan H Kuijper[SUP] 1 2 [/SUP], Laura Y L Kummer[SUP] 1 2 3 [/SUP], Laura Fernandez Blanco[SUP] 1 2 3 [/SUP], Karlijn van der Straten[SUP] 2 4 [/SUP], Mathieu A F Claireaux[SUP] 2 4 [/SUP], Amélie V Bos[SUP] 1 2 [/SUP], Miranda C Dieker-Meijer[SUP] 1 2 [/SUP], Tineke Jorritsma[SUP] 1 2 [/SUP], Mariël C Duurland[SUP] 1 2 [/SUP], Maurice Steenhuis[SUP] 1 2 [/SUP], Juan J Garcia Vallejo[SUP] 2 5 [/SUP], Koos P J van Dam[SUP] 3 [/SUP], Eileen W Stalman[SUP] 3 [/SUP], Luuk Wieske[SUP] 3 6 [/SUP], Sander W Tas[SUP] 2 7 [/SUP], Laura Boekel[SUP] 2 8 [/SUP], Gert-Jan Wolbink[SUP] 2 8 [/SUP], Theo Rispens[SUP] 1 2 [/SUP], Taco W Kuijpers[SUP] 2 9 [/SUP], Filip Eftimov[SUP] 3 [/SUP], Marit J van Gils[SUP] 2 4 [/SUP], Anja Ten Brinke[SUP] 1 2 [/SUP], S Marieke van Ham[SUP] 1 2 10 [/SUP]; T2B! immunity against SARS‐CoV‐2 study group
Affiliations
After antigen encounter, long-lived antibody-secreting cells (ASC) secrete high-affinity circulating antibodies. In addition, memory B cells (MBC) are quickly reactivated upon antigen re-exposure and predominantly generate shorter-lived ASCs. Studies have suggested that MBC can differentiate into ASCs without recognizing their cognate antigen, a process known as "bystander activation". This antigen-independent reactivation of MBC could help maintain circulating antibody levels, thereby protecting against future infections. To elucidate whether SARS-CoV-2 mRNA vaccination leads to bystander activation of B cells, the dynamics of antibody concentrations against six pathogen-specific antigens not encountered during the sampling period were analyzed over time. Deep profiling of antigen-specific B cell responses was simultaneously performed using multiparameter high-dimensional spectral flow cytometry. Antibody concentrations against tetanus toxoid (TT), respiratory syncytial virus (RSV), and influenza hemagglutinin (HA) unexpectedly increased 6 weeks after the first SARS-CoV-2 vaccination. Deep profiling of B cell differentiation stages demonstrated a short-term increase in influenza-specific IgG+ DN3 B cells, RSV-specific IgG+ CD11c+ activated B cells, and TT-specific IgG+ MBC following vaccination. In this study, we demonstrated at both the antibody and cellular levels that SARS-CoV-2 mRNA vaccination transiently activates distinct early activated B cell compartments directed against influenza HA, RSV, and TT.
Keywords: DN3; IgG+ activated B cells; antibodies; antibody‐secreting cells; memory B cells; noncognate antigen; serological memory.
. 2026 Jan;56(1):e70127.
doi: 10.1002/eji.70127. SARS-CoV-2 mRNA Vaccination Leads to Transient Humoral and B Cell Bystander Responses in Adults
Lisan H Kuijper[SUP] 1 2 [/SUP], Laura Y L Kummer[SUP] 1 2 3 [/SUP], Laura Fernandez Blanco[SUP] 1 2 3 [/SUP], Karlijn van der Straten[SUP] 2 4 [/SUP], Mathieu A F Claireaux[SUP] 2 4 [/SUP], Amélie V Bos[SUP] 1 2 [/SUP], Miranda C Dieker-Meijer[SUP] 1 2 [/SUP], Tineke Jorritsma[SUP] 1 2 [/SUP], Mariël C Duurland[SUP] 1 2 [/SUP], Maurice Steenhuis[SUP] 1 2 [/SUP], Juan J Garcia Vallejo[SUP] 2 5 [/SUP], Koos P J van Dam[SUP] 3 [/SUP], Eileen W Stalman[SUP] 3 [/SUP], Luuk Wieske[SUP] 3 6 [/SUP], Sander W Tas[SUP] 2 7 [/SUP], Laura Boekel[SUP] 2 8 [/SUP], Gert-Jan Wolbink[SUP] 2 8 [/SUP], Theo Rispens[SUP] 1 2 [/SUP], Taco W Kuijpers[SUP] 2 9 [/SUP], Filip Eftimov[SUP] 3 [/SUP], Marit J van Gils[SUP] 2 4 [/SUP], Anja Ten Brinke[SUP] 1 2 [/SUP], S Marieke van Ham[SUP] 1 2 10 [/SUP]; T2B! immunity against SARS‐CoV‐2 study group
Affiliations
- PMID: 41502006
- PMCID: PMC12779779
- DOI: 10.1002/eji.70127
After antigen encounter, long-lived antibody-secreting cells (ASC) secrete high-affinity circulating antibodies. In addition, memory B cells (MBC) are quickly reactivated upon antigen re-exposure and predominantly generate shorter-lived ASCs. Studies have suggested that MBC can differentiate into ASCs without recognizing their cognate antigen, a process known as "bystander activation". This antigen-independent reactivation of MBC could help maintain circulating antibody levels, thereby protecting against future infections. To elucidate whether SARS-CoV-2 mRNA vaccination leads to bystander activation of B cells, the dynamics of antibody concentrations against six pathogen-specific antigens not encountered during the sampling period were analyzed over time. Deep profiling of antigen-specific B cell responses was simultaneously performed using multiparameter high-dimensional spectral flow cytometry. Antibody concentrations against tetanus toxoid (TT), respiratory syncytial virus (RSV), and influenza hemagglutinin (HA) unexpectedly increased 6 weeks after the first SARS-CoV-2 vaccination. Deep profiling of B cell differentiation stages demonstrated a short-term increase in influenza-specific IgG+ DN3 B cells, RSV-specific IgG+ CD11c+ activated B cells, and TT-specific IgG+ MBC following vaccination. In this study, we demonstrated at both the antibody and cellular levels that SARS-CoV-2 mRNA vaccination transiently activates distinct early activated B cell compartments directed against influenza HA, RSV, and TT.
Keywords: DN3; IgG+ activated B cells; antibodies; antibody‐secreting cells; memory B cells; noncognate antigen; serological memory.