Work

The B cell dilemma: Diversity or fidelity?

Year: 2025

Type: article

Abstract: The ability of B lymphocytes to diversify immunoglobulin (Ig) genes is central to the generation of high-affinity, class-switched antibodies and the establishment of effective humoral immunity. This diversification is achieved through three DNA remodeling processes that occur at defined stages of B cell development and maturation: V(D)J recombination, somatic hypermutation (SHM), and class switch recombination (CSR). These reactions all rely on the induction of programmed DNA lesions at Ig genes and their productive resolution by ubiquitous DNA repair pathways. However, such physiological sources of genotoxic stress render B cells vulnerable to genome instability, including mutations and chromosomal translocations that drive malignancies. Therefore, B cells have evolved complex regulatory networks that ensure efficient Ig gene diversification while minimizing the risk of unproductive or deleterious repair outcomes. In this review, we integrate foundational studies with recent mechanistic advances to outline how B cells exploit, coordinate, and constrain DNA repair to balance immune receptor diversification with the preservation of genome integrity.

Source: DNA repair

DOI: 10.1016/j.dnarep.2025.103888

Authors: Maria Berruezo-Llacuna, Eleni Kabrani, Michela Di Virgilio

Institutions: Max Delbrück Center, Aristotle University of Thessaloniki, Charité - Universitätsmedizin Berlin

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,390