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Intoduction: Two scaffold/matrix attachment regions (5'- and 3'- MARs Eµ ) flank the intronic core enhancer (c Eµ ) within the immunoglobulin heavy chain locus ( IgH ). Besides their conservation in mice and humans, the physiological role of MARs Eµ is still unclear and their involvement in somatic hypermutation (SHM) has never been deeply evaluated., Methods: Our study analyzed SHM and its transcriptional control in a mouse model devoid of MARs Eµ , further combined to relevant models deficient for base excision repair and mismatch repair., Results: We observed an inverted substitution pattern in of MARs Eµ -deficient animals: SHM being decreased upstream from c Eµ and increased downstream of it. Strikingly, the SHM defect induced by MARs Eµ -deletion was accompanied by an increase of sense transcription of the IgH V region, excluding a direct transcription-coupled effect. Interestingly, by breeding to DNA repair-deficient backgrounds, we showed that the SHM defect, observed upstream from c Eµ in this model, was not due to a decrease in AID deamination but rather the consequence of a defect in base excision repair-associated unfaithful repair process., Discussion: Our study pointed out an unexpected "fence" function of MARs Eµ regions in limiting the error-prone repair machinery to the variable region of Ig gene loci., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martin, Thomas, Marquet, Bruzeau, Garot, Brousse, Bender, Carrion, Choi, Vuong, Gearhart, Maul, Le Noir and Pinaud.)

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4 + pre-T follicular helper (pre-Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B cells in the EF and GC response. Overall, these studies demonstrate that B cells expressing high affinity BCRs preferentially differentiate into antibody secreting cells (ASCs) while those expressing low affinity BCRs undergo further affinity maturation or differentiate into memory B cells (MBCs)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wishnie, Chwat-Edelstein, Attaway and Vuong.)