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Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network
Author(s) -
Igarashi Kazuhiko,
Ochiai Kyoko,
ItohNakadai Ari,
Muto Akihiko
Publication year - 2014
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12201
Subject(s) - biology , cytidine deaminase , somatic hypermutation , transcription factor , repressor , microbiology and biotechnology , immunoglobulin class switching , cellular differentiation , regulation of gene expression , b cell , gene , genetics , antibody
Summary Bach2 is a basic region‐leucine zipper (bZip) transcription factor that forms heterodimers with small Maf oncoproteins and binds to target genes, thus repressing their expression. Bach2 is required for class switch recombination ( CSR ) and somatic hypermutation ( SHM ) of immunoglobulin genes in activated B cells. Bach2 represses the expression of Prdm1 encoding Blimp‐1 repressor and thereby inhibits terminal differentiation of B cells to plasma cells. This causes a delay in the induction of Prdm1 , thereby securing a time window for the expression of Aicda encoding activation‐induced cytidine deaminase ( AID ) required for both CSR and SHM . Based on the characteristics of a gene regulatory network ( GRN ) involving Bach2 and Prdm1 and its dynamics, a ‘delay‐driven diversity’ model was introduced to explain the responses of activated B cells. Bach2 is also required for the proper differentiation and function of peripheral T cells. In the absence of Bach2, CD 4 + T cells show increased differentiation to effector cells producing higher levels of Th2‐related cytokines, such as IL‐4 and IL‐10, and a reduction in the generation of regulatory T cells. Bach2 represses many genes in T cells, including Prdm1, suggesting that the Bach2 ‐ Prdm1 pathway is also important in maintaining the homeostasis of T cells. Furthermore, Bach2 is essential for the function of alveolar macrophages. Therefore, Bach2 orchestrates both acquired and innate immunity at multiple points. Its connection with disease is also reviewed in this report.