» Articles » PMID: 28393923

Altered B Cell Signalling in Autoimmunity

Overview
Journal Nat Rev Immunol
Date 2017 Apr 11
PMID 28393923
Citations 145
Authors
Affiliations
Soon will be listed here.
Abstract

Recent work has provided new insights into how altered B cell-intrinsic signals - through the B cell receptor (BCR) and key co-receptors - function together to promote the pathogenesis of autoimmunity. These combined signals affect B cells at two distinct stages: first, in the selection of the naive repertoire; and second, during extrafollicular or germinal centre activation responses. Thus, dysregulated signalling can lead to both an altered naive BCR repertoire and the generation of autoantibody-producing B cells. Strikingly, high-affinity autoantibodies predate and predict disease in several autoimmune disorders, including type 1 diabetes and systemic lupus erythematosus. This Review summarizes how, rather than being a downstream consequence of autoreactive T cell activation, dysregulated B cell signalling can function as a primary driver of many human autoimmune diseases.

Citing Articles

Acquired drivers of C3 glomerulopathy.

Welsh S, Zhang Y, Smith R Clin Kidney J. 2025; 18(3):sfaf022.

PMID: 40052168 PMC: 11883229. DOI: 10.1093/ckj/sfaf022.


IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints.

Fike A, Bricker K, Gonzalez M, Maharjan A, Bui T, Nuon K bioRxiv. 2025; .

PMID: 39974943 PMC: 11838595. DOI: 10.1101/2025.02.04.636277.


TCL1A in naïve B cells as a therapeutic target for type 1 diabetes.

Luo S, Zhang L, Wei C, Guo C, Meng Z, Zeng H EBioMedicine. 2025; 113:105593.

PMID: 39946833 PMC: 11872515. DOI: 10.1016/j.ebiom.2025.105593.


Organ-based characterization of B cells in patients with systemic lupus erythematosus.

Wang Y, Zhao R, Liang Q, Ni S, Yang M, Qiu L Front Immunol. 2025; 16:1509033.

PMID: 39917309 PMC: 11798990. DOI: 10.3389/fimmu.2025.1509033.


Permissive central tolerance plus defective peripheral checkpoints licence pathogenic memory B cells in CASPR2-antibody encephalitis.

Sun B, Fernandes D, Kienzler A, Paneva S, Harrison R, Ramanathan S bioRxiv. 2025; .

PMID: 39868113 PMC: 11760777. DOI: 10.1101/2025.01.14.631703.


References
1.
Soni C, Wong E, Domeier P, Khan T, Satoh T, Akira S . B cell-intrinsic TLR7 signaling is essential for the development of spontaneous germinal centers. J Immunol. 2014; 193(9):4400-14. PMC: 4201954. DOI: 10.4049/jimmunol.1401720. View

2.
Otipoby K, Waisman A, Derudder E, Srinivasan L, Franklin A, Rajewsky K . The B-cell antigen receptor integrates adaptive and innate immune signals. Proc Natl Acad Sci U S A. 2015; 112(39):12145-50. PMC: 4593120. DOI: 10.1073/pnas.1516428112. View

3.
Begovich A, Carlton V, Honigberg L, Schrodi S, Chokkalingam A, Alexander H . A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet. 2004; 75(2):330-7. PMC: 1216068. DOI: 10.1086/422827. View

4.
Martin F, Kearney J . Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk. Immunity. 2000; 12(1):39-49. DOI: 10.1016/s1074-7613(00)80157-0. View

5.
Poholek A, Hansen K, Hernandez S, Eto D, Chandele A, Weinstein J . In vivo regulation of Bcl6 and T follicular helper cell development. J Immunol. 2010; 185(1):313-26. PMC: 2891136. DOI: 10.4049/jimmunol.0904023. View