tetano
Editor, Senior Moderator
Eur J Immunol
. 2026 Mar;56(3):e70165.
doi: 10.1002/eji.70165.
Heterogeneous Activated B Cell Compartments Arising Early and Transiently After SARS-CoV-2 Vaccination
Laura Fernandez Blanco[SUP] 1 2 [/SUP], Lisan H Kuijper[SUP] 1 [/SUP], Laura Y L Kummer[SUP] 1 2 [/SUP], Niels J M Verstegen[SUP] 1 [/SUP], Amélie Bos[SUP] 1 [/SUP], Mathieu Claireaux[SUP] 3 [/SUP], Mariël C Duurland[SUP] 1 [/SUP], Tineke Jorritsma[SUP] 1 [/SUP], Maurice Steenhuis[SUP] 1 [/SUP], Gius Kerster[SUP] 3 [/SUP], Juan J Garcia Vallejo[SUP] 4 [/SUP], Marit J van Gils[SUP] 3 [/SUP], Koos P J van Dam[SUP] 2 [/SUP], Eileen W Stalman[SUP] 2 [/SUP], Luuk Wieske[SUP] 5 [/SUP], Laura Boekel[SUP] 6 [/SUP], Gertjan J Wolbink[SUP] 6 [/SUP], Sander W Tas[SUP] 7 [/SUP], Theo Rispens[SUP] 1 [/SUP], Taco W Kuijpers[SUP] 8 [/SUP], Filip Eftimov[SUP] 2 [/SUP], Anja Ten Brinke[SUP] 1 [/SUP], S Marieke van Ham[SUP] 1 9 [/SUP]; of T2B! Immunity Against SARS‐CoV‐2 Study Group
Affiliations
In humans, the stages and dynamics of B cell development after antigen encounter remain unclear. Identifying early B cell differentiation stages could reveal biomarkers for humoral immunity and potential targets to prevent unwanted antibody responses. We characterized antigen-specific B cell responses longitudinally after SARS-CoV-2 mRNA vaccination using multiparameter spectral flow cytometry. Spike-specific IgG[SUP]+[/SUP] CD27[SUP]+[/SUP] CD71[SUP]+[/SUP] activated B cells (ActBCs), presumed to be germinal center-derived and IgG[SUP]+[/SUP] DN2 extrafollicular B cells, dominated the early antigen-specific B cell response, while memory B cells were the main population 6 months after vaccination. Within the IgG[SUP]+[/SUP] ActBC compartment, we delineated six novel clusters with specific contraction dynamics. Following the second vaccination, certain ActBC clusters displayed sustained expansion over time, being phenotypically similar to memory B cells, while others strongly expanded and subsequently contracted. Several of the rapidly contracting ActBC clusters expressed CD11c, a defining marker for atypical B cells, suggesting a possible extrafollicular origin of these clusters. The transient presence of heterogeneous ActBC clusters was also observed for total B cells when gated in an antigen-independent manner. Characterization of novel ActBC clusters early after antigen encounter helps delineate and dissect the complexity of B cell differentiation, which is vital for understanding unwanted B cell responses.
Keywords: B‐cell differentiation; CD11c+ activated B cells; extrafollicular responses; germinal center; immunological memory; mRNA vaccination.
. 2026 Mar;56(3):e70165.
doi: 10.1002/eji.70165.
Heterogeneous Activated B Cell Compartments Arising Early and Transiently After SARS-CoV-2 Vaccination
Laura Fernandez Blanco[SUP] 1 2 [/SUP], Lisan H Kuijper[SUP] 1 [/SUP], Laura Y L Kummer[SUP] 1 2 [/SUP], Niels J M Verstegen[SUP] 1 [/SUP], Amélie Bos[SUP] 1 [/SUP], Mathieu Claireaux[SUP] 3 [/SUP], Mariël C Duurland[SUP] 1 [/SUP], Tineke Jorritsma[SUP] 1 [/SUP], Maurice Steenhuis[SUP] 1 [/SUP], Gius Kerster[SUP] 3 [/SUP], Juan J Garcia Vallejo[SUP] 4 [/SUP], Marit J van Gils[SUP] 3 [/SUP], Koos P J van Dam[SUP] 2 [/SUP], Eileen W Stalman[SUP] 2 [/SUP], Luuk Wieske[SUP] 5 [/SUP], Laura Boekel[SUP] 6 [/SUP], Gertjan J Wolbink[SUP] 6 [/SUP], Sander W Tas[SUP] 7 [/SUP], Theo Rispens[SUP] 1 [/SUP], Taco W Kuijpers[SUP] 8 [/SUP], Filip Eftimov[SUP] 2 [/SUP], Anja Ten Brinke[SUP] 1 [/SUP], S Marieke van Ham[SUP] 1 9 [/SUP]; of T2B! Immunity Against SARS‐CoV‐2 Study Group
Affiliations
- PMID: 41817302
- PMCID: PMC12981206
- DOI: 10.1002/eji.70165
In humans, the stages and dynamics of B cell development after antigen encounter remain unclear. Identifying early B cell differentiation stages could reveal biomarkers for humoral immunity and potential targets to prevent unwanted antibody responses. We characterized antigen-specific B cell responses longitudinally after SARS-CoV-2 mRNA vaccination using multiparameter spectral flow cytometry. Spike-specific IgG[SUP]+[/SUP] CD27[SUP]+[/SUP] CD71[SUP]+[/SUP] activated B cells (ActBCs), presumed to be germinal center-derived and IgG[SUP]+[/SUP] DN2 extrafollicular B cells, dominated the early antigen-specific B cell response, while memory B cells were the main population 6 months after vaccination. Within the IgG[SUP]+[/SUP] ActBC compartment, we delineated six novel clusters with specific contraction dynamics. Following the second vaccination, certain ActBC clusters displayed sustained expansion over time, being phenotypically similar to memory B cells, while others strongly expanded and subsequently contracted. Several of the rapidly contracting ActBC clusters expressed CD11c, a defining marker for atypical B cells, suggesting a possible extrafollicular origin of these clusters. The transient presence of heterogeneous ActBC clusters was also observed for total B cells when gated in an antigen-independent manner. Characterization of novel ActBC clusters early after antigen encounter helps delineate and dissect the complexity of B cell differentiation, which is vital for understanding unwanted B cell responses.
Keywords: B‐cell differentiation; CD11c+ activated B cells; extrafollicular responses; germinal center; immunological memory; mRNA vaccination.