Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification.

Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification. Adv Immunol. 2019;141:51-103 Authors: Yeap LS, Meng FL Abstract Antigen receptor diversification is a hallmark of adaptive immunity which allows specificity of the receptor to particular antigen. B cell receptor (BCR) or its secreted form, antibody, is diversified through antigen-independent and antigen-dependent mechanisms. During B cell development in bone marrow, BCR is diversified via V(D)J recombination mediated by RAG endonuclease. Upon stimulation by antigen, B cell undergo somatic hypermutation (SHM) to allow affinity maturation and class switch recombination (CSR) to change the effector function of the antibody. Both SHM and CSR are initiated by activation-induced cytidine deaminase (AID). Repair of AID-initiated lesions through different DNA repair pathways results in diverse mutagenic outcomes. Here, we focus on discussing cis- and trans-factors that target AID to its substrates and factors that affect different outcomes of AID-initiated lesions. The knowledge of mechanisms that govern AID targeting and outcomes could be harnessed to elicit rare functional antibodies and develop ex vivo antibody diversification approaches with diversifying base editors. PMID: 30904133 [PubMed - in process]
Source: Advances in Immunology - Category: Allergy & Immunology Authors: Tags: Adv Immunol Source Type: research