A Spatiotemporal Map of Co-Receptor Signaling Networks Underlying B Cell Activation

Authors

Katherine J Susa
Gary A Bradshaw
Robyn J Eisert
Charlotte M Schilling
Marian Kalocsay
Stephen C Blacklow
Andrew C Kruse

Publication Date

6-25-2024

Journal

Cell Reports

Abstract

The B cell receptor (BCR) signals together with a multi-component co-receptor complex to initiate B cell activation in response to antigen binding. Here, we take advantage of peroxidase-catalyzed proximity labeling combined with quantitative mass spectrometry to track co-receptor signaling dynamics in Raji cells from 10 s to 2 h after BCR stimulation. This approach enables tracking of 2,814 proximity-labeled proteins and 1,394 phosphosites and provides an unbiased and quantitative molecular map of proteins recruited to the vicinity of CD19, the signaling subunit of the co-receptor complex. We detail the recruitment kinetics of signaling effectors to CD19 and identify previously uncharacterized mediators of B cell activation. We show that the glutamate transporter SLC1A1 is responsible for mediating rapid metabolic reprogramming and for maintaining redox homeostasis during B cell activation. This study provides a comprehensive map of BCR signaling and a rich resource for uncovering the complex signaling networks that regulate activation.

Keywords

Humans, Signal Transduction, B-Lymphocytes, Receptors, Antigen, B-Cell, Lymphocyte Activation, Antigens, CD19, Cell Line, Tumor, Oxidation-Reduction

Comments

Supplementary Materials

PMID: 38850533