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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 1 2 , Lisan H Kuijper 1 , Laura Y L Kummer 1 2 , Niels J M Verstegen 1 , Amélie Bos 1 , Mathieu Claireaux 3 , Mariël C Duurland 1 , Tineke Jorritsma 1 , Maurice Steenhuis 1 , Gius Kerster 3 , Juan J Garcia Vallejo 4 , Marit J van Gils 3 , Koos P J van Dam 2 , Eileen W Stalman 2 , Luuk Wieske 5 , Laura Boekel 6 , Gertjan J Wolbink 6 , Sander W Tas 7 , Theo Rispens 1 , Taco W Kuijpers 8 , Filip Eftimov 2 , Anja Ten Brinke 1 , S Marieke van Ham 1 9 ; 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+ CD27+ CD71+ activated B cells (ActBCs), presumed to be germinal center-derived and IgG+ 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+ 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 1 2 , Lisan H Kuijper 1 , Laura Y L Kummer 1 2 , Niels J M Verstegen 1 , Amélie Bos 1 , Mathieu Claireaux 3 , Mariël C Duurland 1 , Tineke Jorritsma 1 , Maurice Steenhuis 1 , Gius Kerster 3 , Juan J Garcia Vallejo 4 , Marit J van Gils 3 , Koos P J van Dam 2 , Eileen W Stalman 2 , Luuk Wieske 5 , Laura Boekel 6 , Gertjan J Wolbink 6 , Sander W Tas 7 , Theo Rispens 1 , Taco W Kuijpers 8 , Filip Eftimov 2 , Anja Ten Brinke 1 , S Marieke van Ham 1 9 ; 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+ CD27+ CD71+ activated B cells (ActBCs), presumed to be germinal center-derived and IgG+ 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+ 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.