Cell Rep . Memory B cells targeting SARS-CoV-2 spike protein and their dependence on CD4 + T cell help

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Cell Rep


. 2021 Jun 11;109320.
doi: 10.1016/j.celrep.2021.109320. Online ahead of print.
Memory B cells targeting SARS-CoV-2 spike protein and their dependence on CD4 ⁺ T cell help


Jernej Pušnik ¹ , Enrico Richter ¹ , Bianca Schulte ¹ , Ramona Dolscheid-Pommerich ² , Christian Bode ³ , Christian Putensen ³ , Gunther Hartmann ² , Galit Alter ⁴ , Hendrik Streeck ⁵



Affiliations

• PMID: 34146478
• DOI: 10.1016/j.celrep.2021.109320

Abstract

Memory B cells seem to be more durable than antibodies and thus crucial for the long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here we investigate SARS-CoV-2 spike-specific memory B cells and their dependence on CD4⁺ T cell help in different settings of coronavirus disease 2019 (COVID-19). Compared with severely ill individuals, those who recovered from mild COVID-19 develop fewer but functionally superior spike-specific memory B cells. Generation and affinity maturation of these cells is best associated with IL-21⁺CD4⁺ T cells in recovered individuals and CD40L⁺CD4⁺ T cells in severely ill individuals. The increased activation and exhaustion of memory B cells observed during COVID-19 correlates with CD4⁺ T cell functions. Intriguingly, CD4⁺ T cells recognizing membrane protein show a stronger association with spike-specific memory B cells than those recognizing spike or nucleocapsid proteins. Overall, we identify CD4⁺ T cell subsets associated with the generation of B cell memory during SARS-CoV-2 infection.

Keywords: CD4(+) T cell; CD40L; COVID-19; IL-21; SARS-CoV-2; antibody; memory B cells; recovered; severely ill; spike.