REAGENT or RESOURCE AVAILABILITY	SOURCE	IDENTIFIER
Antibodies
P5C3 human monoclonal antibody	This paper	N/A
Mouse anti-human CD19 APC-Cy7	BD Biosciences	Cat#557791, RRID: AB_396873
Mouse anti-human CD3-BV510	BD Biosciences	Cat#563109, RRID: AB_2732053
Mouse anti-human IgM-FITC	Biolegend	Cat#314506, RRID: AB_493009
Mouse anti-human IgD PE-CF594	BD Biosciences	Cat#562540, RRID: AB_11153129
Mouse anti-human CD27-APC	BD Biosciences	Cat#558664; RRID: AB_1645457
Mouse anti-human CD38-V450	BD Biosciences	Cat#646851, RRID: AB_1937282
REGN10987	Hansen et al., 2020b	N/A
REGN10933	Hansen et al., 2020b	N/A
S309	Pinto et al., 2020	N/A
Bacterial and virus strains
SARS-CoV-2	Geneva University Hospitals	hCoV-19/Switzerland/ GE9586
SARS-Cov-2 Mink-related variant	Statens Serum Institute	hCoV-19/Denmark/ DCGC-9495/2020
SARS-Cov2 recombinant clone D614G	Institute of virology and immunology (Thi Nhu Thao et al., 2020)	N/A
SARS-Cov2 recombinant clone B1.1.7	Institute of virology and immunology	N/A
SARS-Cov2 recombinant clone B1.351 Spike	Institute of virology and immunology	N/A
NEB 5-alpha High Efficiency Competent E. coli bacteria	New England Biolabs	Cat# C2987H
Chemicals, peptides, and recombinant proteins
Recombinant trimeric Spike of SARS-Cov-2	Fenwick et al., 2021b	N/A
Recombinant trimeric Spike variants	This paper and Fenwick et al. (2021b)	N/A
D-desthiobiotin	Sigma	Cat#71610
RPMI medium	GIBCO, Life Technologies	Cat#61870-010
GlutaMAX™ supplement	ThermoFisher	Cat#35050061
Penicillin-Streptomycin	GIBCO, Life Technologies	Cat#15070-063
Fetal Bovine Serum (FBS)	ThermoFisher	Cat#10500064
Minimum Essential Medium Eagle	Sigma Aldrich	Cat#M2279
MEM Non-Essential Amino Acids Solution	GIBCO, Life Technologies	Cat#11140050
PEI MAX	Polysciences	Cat#49553-93-7
ProCHO5 medium	Lonza	Cat#BELN12-766Q
Human IL-2	Miltenyi Biotec	Cat#130-097-742
Human IL-21	Miltenyi Biotec	Cat#130-095-768
Human IL6	Miltenyi Biotec	Cat#130-095-352
TLR9 agonist CpG 2006	Invivogen	Cat#tlrl-2006
2-bêta-mercaptoethanol	Sigma	Cat#M6250-10ML
Critical commercial assays
HIV p24 antigen ELISA	Zeptometrix	Cat#0801111
ONE-step Luciferase assay	BPS Bioscience	Cat#60690
Deposited data
Structural model: Full spike with P5C3 Fab	PDB	PDB ID: 7P40 EMD-13190
Structural model: Local refinement RBD+Fab	PDB	PDB ID: 7PHG EMD-13415
Experimental model and subject details
Experimental models: Cell lines
Human embryonic kidney cells (HEK293T)	ATCC	Cat#CRL-3216, RRID:CVCL_0063
ExpiCHO cells	ThermoFischer	Cat#A29127, RRID:CVCL_5J31
VeroE6	ATCC	Cat#CRL-1586, RRID:CVCL_0574
B95-8 cells	ATCC	Cat#CRL-1612, RRID:CVCL_1953
3T3ms CD40L cells	NIH AIDS	Cat#12535, RRID:CVCL_1H10
HEK293T_ACE2	This paper and Fenwick et al. (2021b)	N/A
Oligonucleotides
For recombinant trimeric Spikes constructs	Fenwick et al., 2021b	N/A
L452R recombinant trimeric Spike	This paper, microsynth	N/A
Recombinant DNA
pCDH-EF1-MCS	System Biosciences	Cat#CD502A-1
pMD2.G	D. Trono	Addgene, Cat#12259, RRID:Addgene_12259
psPAX2	D. Trono	Addgene, Cat#12260, RRID:Addgene_12260
pCAGGS-SARS2-S D614G	Wang et al., 2021a	N/A
pMDL p.RRE	D.Trono	Addgene, Cat#12251
pRSV.Rev	D. Trono	Addgene, Cat#12253
pUltra-Chili-Luc vectors	M. Moore	Addgene, Cat#48688, RRID:Addgene_48688
pHAGE2-CMV-Luc-ZSgreen, Hgpm2, REV1b and Tat1b	Crawford et al., 2020	N/A
HDM-IDTSpike-fixK	Crawford et al., 2020	BEI NR-52514
HDM-IDTSpike-fixK-mutants	Fenwick et al., 2021b	N/A
2019-nCoV plasmid	Wrapp et al., 2020b	N/A
2019-nCoV mutants plasmids	This paper and Fenwick et al. (2021b)	N/A
Experimental models: Animal models
Female hFcRn Tg32 mice of 12 weeks age.	Jackson laboratory	Stock No.014565
Female wild-type Syrian Golden hamsters (Mesocricetus auratus) 6 to 8 weeks of age.	Janvier Laboratories	Syrian Golden hamsters
COVID-19 patient biological samples
B cells specific for SARS-CoV-2 Spike	Patient specific	ImmunoCov study
Software and algorithms
FlowJo v10	FlowJo, LLC	https://www.flowjo.com/solutions/flowjo
GraphPad Prism 8.3.0	GraphPad	https://www.graphpad.com/
BioTek Gen5 v.3.0.3	BioTek	https://www.biotek.com/products/get-info/gen5-get-info.html
cryoSPARC v.3.0. 1	Punjani et al., 2017	https://cryosparc.com/
COOT	Emsley et al., 2010	https://www2.mrc-lmb.cam.ac.uk/personal/pemsley/coot/
UCSF Chimera	Pettersen et al., 2004	http://www.cgl.ucsf.edu/chimera/index.html
PHENIX	Adams et al., 2010	https://phenix-online.org/documentation/index.html
EM RINGER	Barad et al., 2015	https://github.com/fraser-lab/EMRinger
UCSF ChimeraX	Goddard et al., 2018	https://www.rbvi.ucsf.edu/chimerax/
Pymol	Schrödinger	https://pymol.org/2/
ImageJ software	National Institutes of Health	https://imagej.nih.gov
Other
Streptactin	IBA	Cat#15728207
StrepTrap HP	Cytiva	Cat#28907546
Streptavidin-PE	BD Biosciences	Cat# 554061; RRID: AB_10053328
Live/Dead Cell staining - Aqua	Invitrogen	Cat#L34965