SARS-CoV-2 sculpts immune system to induce sustained virus-specific naïve-like and memory B cell responses

 Leire de Campos-Mata, Sonia Tejedor Vaquero, Roser Tachó-Piñot, Janet Piñero, Emilie K. Grasset, Itziar Arrieta Aldea, Natalia Rodrigo Melero, Carlo Carolis, Juan P. Horcajada, Andrea Cerutti, Judit Villar-García,  

View ORCID ProfileGiuliana Magri

doi: https://doi.org/10.1101/2021.04.29.21256002

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.29.21256002v1.full.pdf

Abstract

SARS-CoV-2 infection induces virus-reactive memory B cells expressing unmutated antibodies, which hints at their emergence from naïve B cells. Yet, the dynamics of virus-specific naïve B cells and their impact on immunity and immunopathology remain unclear. Here, we longitudinally studied moderate to severe COVID-19 patients to dissect SARS-CoV-2-specific B cell responses overtime. We found a broad virus-specific antibody response during acute infection, which evolved into an IgG1-dominated response during convalescence. Acute infection was associated with increased mature B cell progenitors in the circulation and the unexpected expansion of virus-targeting naïve-like B cells that further augmented during convalescence together with virus-specific memory B cells. In addition to a transitory increase in tissue-homing CXCR3+ plasmablasts and extrafollicular memory B cells, most COVID-19 patients showed persistent activation of CD4+ and CD8+ T cells along with transient or long-lasting changes of key innate immune cells. Remarkably, virus-specific antibodies and the frequency of naïve B cells were among the major variables defining distinct immune signatures associated with disease severity and inflammation. Aside from providing new insights into the complexity of the immune response to SARS-CoV-2, our findings indicate that the de novo recruitment of mature B cell precursors into the periphery may be central to the induction of antiviral immunity.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

We want to particularly acknowledge the patients and the Parc de Salut Mar MARBiobanc (PT17/0015/0011) integrated in the Spanish National Biobanks Network from ISCIII for their collaboration. MARBiobanc work was supported by grants from Instituto de Salud Carlos III/FEDER (PT17/0015/0011) and the Xarxa de Bancs de tumors sponsored by Pla Director d Oncologia de Catalunya (XBTC). This study was supported by the COVID 19 call grant from Generalitat de Catalunya, Department of Health (to G.M and L.D.C.M) and grant Miguel Servet research program (to G.M). IMI/JU resources of which are composed of financial contribution from the EU/FP7 (FP7 2007/2013) and EFPIA companies in kind contribution (116030 to TransQST, 777365 to eTRANSAFE),and the EU H2020 Programme 2014/2020 (676559 to Elixir-Excelerate); Agencia de Gestio d Ajuts Universitaris i de Recerca Generalitat de Catalunya (2017SGR00519). The Research Programme on Biomedical Informatics (GRIB) is a member of the Spanish National Bioinformatics Institute (INB), funded by ISCIII and FEDER (PRB2/ISCIII (PT13/0001/0023, of the PE I+D+i 2013/2016). The DCEXS is a Unidad de Excelencia Maria de Maeztu, funded by the MINECO (MDM-2014-0370).

https://www.medrxiv.org/content/10.1101/2021.04.29.21256002v1