Mechanism and regulation of class switch recombination by IgH transcriptional control elements

Chloé Oudinet (1) , Fatima-Zohra Braikia (1) , Audrey Dauba (1) , Ahmed Amine Khamlichi (1)

1 IPBS - Institut de pharmacologie et de biologie structurale

Class switch recombination (CSR) plays an important role in humoral immunity by generating antibodies with different effector functions. CSR to a particular antibody isotype is induced by external stimuli, and occurs between highly repetitive switch (S) sequences. CSR requires transcription across S regions, which generates long non-coding RNAs and secondary structures that promote accessibility of S sequences to activation-induced cytidine deaminase (AID). AID initiates DNA double-strand breaks (DSBs) intermediates that are repaired by general DNA repair pathways. Switch transcription is controlled by various regulatory elements, including enhancers and insulators. The current paradigm posits that transcriptional control of CSR involves long-range chromatin interactions between regulatory elements and chromatin loops-stabilizing factors, which promote alignment of partner S regions in a CSR centre (CSRC) and initiation of CSR. In this review, we focus on the role of IgH transcriptional control elements in CSR and the chromatin-based mechanisms underlying this control

Mots clés: Class switch recombination; IgH locus; B lymphocyte; Loop extrusion; Chromatin; Switch transcription; Enhancer; promoter; Insulator; Long-range interactions

Domaines: Immunité adaptative; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Chloé Oudinet, Fatima-Zohra Braikia, Audrey Dauba, Ahmed Amine Khamlichi. Mechanism and regulation of class switch recombination by IgH transcriptional control elements. Advances in immunology, 2020, 147, pp.89 - 137. ⟨10.1016/bs.ai.2020.06.003⟩. ⟨hal-03428266⟩