The transcriptional programme of antibody class switching involves the repressor Bach2.
Activated B cells differentiate to plasma cells to secrete IgM or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins. Diversification of antibody function by CSR is important for humoral immunity. However, it remains unclear how the decision for the bifurcation is made. Bach2 is a B-cell-specific transcription repressor interacting with the small Maf proteins whose expression is high only before the plasma cell stage. Here we show that Bach2 is critical for CSR and somatic hypermutation (SHM) of immunoglobulin genes. Genetic ablation of Bach2 in mice revealed that Bach2 was required for both T-cell-independent and T-cell-dependent IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced IgM, as did wild-type cells, and abundantly expressed Blimp-1 (refs 9, 10) and XBP-1 (ref. 11), critical regulators of the plasmacytic differentiation, indicating that Bach2 was not required for the plasmacytic differentiation itself. However, they failed to undergo efficient CSR. These findings define Bach2 as a key regulator of antibody response and provide an insight into the orchestration of CSR and SHM during plasma cell differentiation.
Muto
Akihiko
A
Department of Biomedical Chemistry and Leukemia Program Project, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan.
Tashiro
Satoshi
S
Nakajima
Osamu
O
Hoshino
Hideto
H
Takahashi
Satoru
S
Sakoda
Eiichirou
E
Ikebe
Dai
D
Yamamoto
Masayuki
M
Igarashi
Kazuhiko
K
D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors; D002454:Cell Differentiation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
D000906:Antibodies; C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors