Related Experiment Video

Updated: Sep 10, 2025

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

Published on: April 20, 2021

MKLN1-dependent GID4/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody

Philip Barbulescu¹, Matthew K Wong¹, Leon Baronian¹

¹Department of Immunology, University of Toronto, Toronto, ON, Canada.

Journal of Immunology (Baltimore, Md. : 1950)

|August 21, 2025

Abstract

None:

C-terminal to LisH (CTLH) E3 ubiquitin ligase complexes regulate a broad range of biological processes and forms separate supramolecular CTLH-MKLN1 and CTLH-WDR26 assemblies possessing distinct substrate specificities. Our previous work revealed that the CTLH complex utilizes the FAM72A substrate adaptor to ubiquitinate and degrade the uracil-DNA glycosylase 2 (UNG2) base excision repair factor. This outcome in B cells permits deoxyuridine mutations catalyzed by activation-induced cytidine deaminase (AID) to persist toward mutational outcomes and drive antibody diversification events. Here, we report that Mkln1-/- mice specifically lacking assembly of CTLH-MKLN1 complexes display reduced somatic hypermutation and class switch recombination frequencies due to increased UNG2, similar to Fam72a-/- mice. Strikingly, Mkln1-/- mice showed increased germinal center B cells and defects during B-cell development, a phenotype not observed in Fam72a-/- mice, suggesting that MKLN1 regulates proteins that are independent of FAM72A. Together, this work identifies that CTLH-MKLN1 ubiquitin E3 ligase complexes are critical in generating effective humoral immune responses and reveals distinctions between FAM72A-dependent and -independent CTLH complex modalities.

Keywords:

B cells C-terminal to LisH UNG2 class switch recombination somatic hypermutation

More Related Videos

Combined Immunofluorescence and DNA FISH on 3D-preserved Interphase Nuclei to Study Changes in 3D Nuclear Organization

Combined Immunofluorescence and DNA FISH on 3D-preserved Interphase Nuclei to Study Changes in 3D Nuclear Organization

Published on: February 3, 2013

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Related Concept Videos

B Cell Activation and Differentiation

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...

Protein Complexes with Interchangeable Parts

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...

Diversity of Antigen Receptors

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...

T Cell Activation and Clonal Selection

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...

Articles linked to this work by shared authors, journal, and citation graph.

An activity-modulated transport route across myelin (TRAM) for motor-driven organelle transfer in oligodendrocytes.

Nature neuroscience·2026

UV-VIS-NIR chemometric screening of broccoli by-products: Decoupling the spatiotemporal heterogeneity of glucosinolates and functional traits.

Food chemistry·2026

CRISPR-mediated targeting of the LMNA c.745C>T mutation enhances survival and cardiac function in congenital muscular dystrophy.

Molecular therapy. Advances·2026

Microbiota Characterization and Bioactive Potential of Broccoli (Brassica oleracea var. italica) By-Products: Implications for Sustainable Antimicrobial Applications.

Foods (Basel, Switzerland)·2026

Targeted KRASG12V Degradation In Vivo Elicits Lung Adenocarcinoma Regression with Subsequent Relapse from Dysregulated Proteolysis.

Cancer research·2026

Distinct volatile profiles of Metschnikowia pulcherrima L672 and Hanseniaspora uvarum L793 determine their antagonistic efficacy against Aspergillus flavus in a dried fig agar model.

International journal of food microbiology·2026

See all related articles