» Articles » PMID: 16719564

B Cell Antigen Receptor Signaling and Internalization Are Mutually Exclusive Events

Overview
Journal PLoS Biol
Specialty Biology
Date 2006 May 25
PMID 16719564
Citations 44
Authors
Affiliations
Soon will be listed here.
Abstract

Engagement of the B cell antigen receptor initiates two concurrent processes, signaling and receptor internalization. While both are required for normal humoral immune responses, the relationship between these two processes is unknown. Herein, we demonstrate that following receptor ligation, a small subpopulation of B cell antigen receptors are inductively phosphorylated and selectively retained at the cell surface where they can serve as scaffolds for the assembly of signaling molecules. In contrast, the larger population of non-phosphorylated receptors is rapidly endocytosed. Each receptor can undergo only one of two mutually exclusive fates because the tyrosine-based motifs that mediate signaling when phosphorylated mediate internalization when not phosphorylated. Mathematical modeling indicates that the observed competition between receptor phosphorylation and internalization enhances signaling responses to low avidity ligands.

Citing Articles

An Integrated Signaling Threshold Initiates IgG Response toward Virus-like Immunogens.

Wholey W, Meyer A, Yoda S, Mueller J, Mathenge R, Chackerian B J Immunol. 2024; 213(8):1061-1075.

PMID: 39212443 PMC: 11458362. DOI: 10.4049/jimmunol.2400101.


Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor-Proximal Proteins with Immunological Functions.

Hoeger S, Drake L, Drake J Immunohorizons. 2024; 8(4):326-338.

PMID: 38625120 PMC: 11066716. DOI: 10.4049/immunohorizons.2400014.


B cell receptor-induced protein dynamics and the emerging role of SUMOylation revealed by proximity proteomics.

Awoniyi L, Cunha D, Sarapulov A, Hernandez-Perez S, Runsala M, Tejeda-Gonzalez B J Cell Sci. 2023; 136(15).

PMID: 37417469 PMC: 10445728. DOI: 10.1242/jcs.261119.


Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells.

Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi E Nat Biotechnol. 2023; 41(9):1229-1238.

PMID: 36658341 PMC: 10354218. DOI: 10.1038/s41587-022-01637-z.


The Ins and Outs of Antigen Uptake in B cells.

McShane A, Malinova D Front Immunol. 2022; 13:892169.

PMID: 35572544 PMC: 9097226. DOI: 10.3389/fimmu.2022.892169.


References
1.
Siemasko K, Eisfelder B, STEBBINS C, Kabak S, Sant A, Song W . Ig alpha and Ig beta are required for efficient trafficking to late endosomes and to enhance antigen presentation. J Immunol. 1999; 162(11):6518-25. View

2.
Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen P, Reth M . SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation. J Exp Med. 1998; 188(4):791-5. PMC: 2213353. DOI: 10.1084/jem.188.4.791. View

3.
Guagliardi L, Koppelman B, Blum J, Marks M, Cresswell P, Brodsky F . Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment. Nature. 1990; 343(6254):133-9. DOI: 10.1038/343133a0. View

4.
Niiro H, Clark E . Branches of the B cell antigen receptor pathway are directed by protein conduits Bam32 and Carma1. Immunity. 2003; 19(5):637-40. DOI: 10.1016/s1074-7613(03)00303-0. View

5.
Brodsky F, Chen C, Knuehl C, Towler M, Wakeham D . Biological basket weaving: formation and function of clathrin-coated vesicles. Annu Rev Cell Dev Biol. 2001; 17:517-68. DOI: 10.1146/annurev.cellbio.17.1.517. View