DOI: 10.5281/zenodo.17603995
title: Single cell BCR data of specific transgenic mouse B cells expressing human HIV-env-targeting BCR variable regions from: Antibody feedback establishes an affinity brake in the germinal center

description: This record contains single cell BCR sequences used in the paper "Antibody feedback establishes an affinity brake in the germinal center (Yan et al. )".

Single cell BCR sequences of heavy or light chain variable regions were aquired using 10x platforms. Sequnces were aquired from specific transgenic mouse B cells expressing human BCR variable regions. BCR variable region sequences involved in this dataset were derived from phylogenetics of human broad neutralizing antibodies targeting 3 different epitopes (CD4bs, V2, V3) of HIV envelope protein and detailed information can be found in the related paper. Experimental information including B cell lineages, timepoints, group names, mice names,sequence ID were included in sequence names for each sequence.

Contributors: Yu Yan1,†, Xuesong Wang1,†, Zhenfei Xie 1,†, Daniel L.  V. Bader2,3,4,7,††, Ryan H. Lim5,6,††, Krystal M. Ma2,4,7, Christopher A. Cottrell2,4,7,  Jon M. Steichen2,4,7, Liling Xu1, Paula Maldonado Villavicencio1, Madhav Akauliya1, Ja-Hyun Koo1, Jacqueline Ming Shen1,9, Alexandra Vernich5,  Oleksandr Kalyuzhniy2,4,7, Joel D. Allen4,8, Ali A. Albowaidey1, Anthony Alicea1, Bingxian Chen1,5,  Erik Georgeson2,4,7, Jordan Renae Ellis-Pugh1, Nushin Alavi2,4,7, Abigail Esposito1, Hannah Naili1, Nicole Phelps2,4,7, Brendon Kelley1, Michael Kubitz2,4,7, Quynh Anh Phan1, Alessia Liguori2,4,7, Thavaleak Prum1, Ryan Tingle2,4,7, Danny Lu2,4,7,  Saman Eskandarzadeh2,4,7, Xiaotie Liu1, John E. Warner1, Stephanie R. Weldon1, Sunny Himansu10, Max Crispin4,8, Usha Nair1, Sophia Liu5,*, William R. Schief2,4,7,10,, Facundo D. Batista1,9,11,12,

1Batista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA 2Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA 3Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA 4Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA 5Liu Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA 6Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology; Cambridge, MA, 02139, USA. 7IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA 8School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK 9Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. 10Moderna Therapeutics, Cambridge, MA 02139, USA 11Department of Immunology, Harvard Medical School, Boston, MA 02115, USA. 12Lead contact †These authors contributed equally. ††These authors contributed equally. *Correspondence: sophia.liu@mgh.harvard.edu (S.L.), schief@scripps.edu (W.R.S.), fbatista1@mgh.harvard.edu (F.D.B.)
description: Recent advances in mRNA vaccine technology have opened the door to novel types of antigen display, but little is yet known as to how B cells recognize and respond to these formats. By delivering an mRNA-LNP encoded membrane-bound immunogen displaying three conserved HIV-1 Envelope (Env) epitopes to knock-in mouse models with B cell receptors (BCRs) of defined affinities, we investigated how epitope-specific competition shapes germinal center (GC) responses. Co-activation of B cells targeting different epitopes did not alter GC kinetics observed in individual activations, but a striking inverse correlation was observed between BCR affinity and GC residence time in either scenario: high-affinity B cells exhibited shorter persistence in GCs, while those with lower affinity to the antigen were maintained. Furthermore, B cells were able to engage in GC reactions at equivalent rates in the presence or absence of clonal lineages binding the same epitope with similar affinities, while higher-affinity clones suppressed lower-affinity counterparts targeting the same epitope. Spatial transcriptomics revealed plasma-like cells within and adjacent to the GC which, together with the detection of early IgG in draining lymph nodes, suggests that local antibody production from these cells may contribute to feedback-driven kinetics. These findings indicate that a self-modulated local antibody feedback loop may act as a “brake” on epitope-specific recognition—dampening further affinity enhancement for high-affinity B cells and facilitating epitope spreading by redirecting the response toward alternative epitopes.