Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19

David G. Priest, Takeshi Ebihara, Janyerkye Tulyeu, Jonas N. Søndergaard, Shuhei Sakakibara, Fuminori Sugihara, Shunichiro Nakao, Yuki Togami, Jumpei Yoshimura, Hiroshi Ito, Shinya Onishi, Arisa Muratsu, Yumi Mitsuyama, Hiroshi Ogura, Jun Oda, Daisuke Okusaki, Hisatake Matsumoto () and James B. Wing ()
Additional contact information
David G. Priest: Osaka University
Takeshi Ebihara: Osaka University
Janyerkye Tulyeu: Osaka University
Jonas N. Søndergaard: Osaka University
Shuhei Sakakibara: Osaka University
Fuminori Sugihara: Osaka University
Shunichiro Nakao: Osaka University Graduate School of Medicine
Yuki Togami: Osaka University Graduate School of Medicine
Jumpei Yoshimura: Osaka University Graduate School of Medicine
Hiroshi Ito: Osaka University Graduate School of Medicine
Shinya Onishi: Osaka University Graduate School of Medicine
Arisa Muratsu: Osaka University Graduate School of Medicine
Yumi Mitsuyama: Osaka University Graduate School of Medicine
Hiroshi Ogura: Osaka University
Jun Oda: Osaka University
Daisuke Okusaki: Osaka University
Hisatake Matsumoto: Osaka University
James B. Wing: Osaka University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Resting memory B cells can be divided into classical or atypical groups, but the heterogenous marker expression on activated memory B cells makes similar classification difficult. Here, by longitudinal analysis of mass cytometry and CITE-seq data from cohorts with COVID-19, bacterial sepsis, or BNT162b2 mRNA vaccine, we observe that resting B cell memory consist of classical CD45RB+ memory and CD45RBlo memory, of which the latter contains of two distinct groups of CD11c+ atypical and CD23+ non-classical memory cells. CD45RB levels remain stable in these cells after activation, thereby enabling the tracking of activated B cells and plasmablasts derived from either CD45RB+ or CD45RBlo memory B cells. Moreover, in both COVID-19 patients and mRNA vaccination, CD45RBlo B cells formed the majority of SARS-CoV2 specific memory B cells and correlated with serum antibodies, while CD45RB+ memory are activated by bacterial sepsis. Our results thus identify that stably expressed CD45RB levels can be exploited to trace resting memory B cells and their activated progeny, and suggest that atypical and non-classical CD45RBlo memory B cells contribute to SARS-CoV-2 infection and vaccination.

Date: 2024
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DOI: 10.1038/s41467-024-50997-4

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