AUTHOR=Bruzeau Charlotte , Cook-Moreau Jeanne , Pinaud Eric , Le Noir Sandrine 

TITLE=Contribution of Immunoglobulin Enhancers to B Cell Nuclear Organization

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.877930

DOI=10.3389/fimmu.2022.877930

ISSN=1664-3224

ABSTRACT=<p>B cells undergo genetic rearrangements at immunoglobulin gene (<italic>Ig</italic>) loci during B cell maturation. First <italic>V(D)J</italic> recombination occurs during early B cell stages followed by class switch recombination (CSR) and somatic hypermutation (SHM) which occur during mature B cell stages. Given that RAG1/2 induces DNA double strand breaks (DSBs) during <italic>V(D)J</italic> recombination and AID (Activation-Induced Deaminase) leads to DNA modifications (mutations during SHM or DNA DSBs during CSR), it is mandatory that <italic>IgH</italic> rearrangements be tightly regulated to avoid any mutations or translocations within oncogenes. Ig loci contain various <italic>cis</italic>-regulatory elements that are involved in germline transcription, chromatin modifications or RAG/AID recruitment. <italic>Ig cis</italic>-regulatory elements are increasingly recognized as being involved in nuclear positioning, heterochromatin addressing and chromosome loop regulation. In this review, we examined multiple data showing the critical interest of studying <italic>Ig</italic> gene regulation at the whole nucleus scale. In this context, we highlighted the essential function of <italic>Ig</italic> gene regulatory elements that now have to be considered as nuclear organizers in B lymphocytes.</p>