The BTB-ZF transcription factor Zbtb20 is driven by Irf4 to promote plasma cell differentiation and longevity.
The transcriptional network regulating antibody-secreting cell (ASC) differentiation has been extensively studied, but our current understanding is limited. The mechanisms of action of known "master" regulators are still unclear, while the participation of new factors is being revealed. Here, we identify Zbtb20, a Bcl6 homologue, as a novel regulator of late B cell development. Within the B cell lineage, Zbtb20 is specifically expressed in B1 and germinal center B cells and peaks in long-lived bone marrow (BM) ASCs. Unlike Bcl6, an inhibitor of ASC differentiation, ectopic Zbtb20 expression in primary B cells facilitates terminal B cell differentiation to ASCs. In plasma cell lines, Zbtb20 induces cell survival and blocks cell cycle progression. Immunized Zbtb20-deficient mice exhibit curtailed humoral responses and accelerated loss of antigen-specific plasma cells, specifically from the BM pool. Strikingly, Zbtb20 induction does not require Blimp1 but depends directly on Irf4, acting at a newly identified Zbtb20 promoter in ASCs. These results identify Zbtb20 as an important player in late B cell differentiation and provide new insights into this complex process.
Molecular Immunology Division, 2 Bioinformatics Division, 3 Immunology Division, The Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia.
Stéphane
S
Chevrier
Dianne
D
Emslie
Wei
W
Shi
Tobias
T
Kratina
Cameron
C
Wellard
Alexander
A
Karnowski
Erdem
E
Erikci
Gordon K
GK
Smyth
Kamal
K
Chowdhury
David
D
Tarlinton
Lynn M
LM
Corcoran
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D051379:Mice; D046228:Microarray Analysis; D010950:Plasma Cells / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000378:metabolism*; D000099218:Interferon Regulatory Factor-4
D001973:Bromodeoxyuridine; D050835:Interferon Regulatory Factors; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C520426:Zbtb20 protein, mouse