AID-induced remodeling of immunoglobulin genes and B cell fate

Abstract

Survival and phenotype of normal and malignant B lymphocytes are critically dependent on constitutive signals by the B cell receptor (BCR) for antigen. In addition, either antigen ligation of the BCR or various mitogenic stimuli result in B cell activation and induction of activation-induced deaminase (AID). AID activity can in turn mediate somatic hypermutation (SHM) of immunoglobulin (Ig) V regions and also deeply remodel the Ig heavy chain locus through class switch recombination (CSR) or locus suicide recombination (LSR). In addition to changes linked to affinity for antigen, modifying the class/isotype (i.e. the structure and function) of the BCR or suddenly deleting BCR expression also modulates the fate of antigen-experienced B cells.

Elucidation of IgH 3′ region regulatory role during class switch recombination via germline deletion

“…Before the occurrence of DSBs, CSR is initiated by AID and the initial outcome of AID targeting can be the occurrence of base substitutions following cytidine deamination 12,14,15,21 . To gain an insight into this initial targeting, we analysed mutations in S regions and observed that both the S m donor and S g1 acceptor regions are less targeted by AID during IgG 1 CSR in 3 0 RR-deficient mice as compared with wt animals (Fig.…”

DC-SIGN–expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma

“…20 The unique cytoplasmic tails of IgM and IgG BCR produce qualitatively different signaling outputs in antigen-experienced B cells. 35 In particular, switched memory B cells are prone to generate a large number of plasma cells whereas IgM 1 memory B cells reinitiate a GC reaction upon antigenic challenge. 36,37 The maintenance of IgM BCR could thus contribute to the frozen GC phenotype of FL B cells that is established very early during lymphomagenesis process and is associated with a high risk of additional genetic events.…”

RNA Exosome and Non-coding RNA-Coupled Mechanisms in AID-Mediated Genomic Alterations

“…Finally, a new AID-dependent recombination event, joining Sμ and switch-like regions located in the 3′RR at the end of the IgH locus, deletes all IgH constant genes and induces B cell apoptosis 27 , again regulating the B cell compartment. So AID and B cell fate are intrinsically linked (for review 28 ) and precise mechanisms governing AID activity, subsequent B cell outcome, and humoral immune responses are important fields of investigation.…”