The BTB-ZF transcription factor Zbtb20 is driven by Irf4 to promote plasma cell differentiation and longevity

Chevrier, Stéphane; Emslie, Dianne; Shi, Wei; Kratina, Tobias; Wellard, Cameron; Karnowski, Alexander; Erikçi, Erdem; Smyth, Gordon K.; Chowdhury, Kamal; Tarlinton, David M.; Corcoran, Lynn M.

doi:10.1084/jem.20131831

Cited by 106 publications

(109 citation statements)

References 60 publications

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“…During this phase of activation, the B cells continue to maintain expression of CXCR5; the balance between CXCL13 expression in the follicles and CCL19/21 expression in the T cell zone positions B cells at the border of the T cell zone [17]. Meanwhile, naive T cells in the T cell zone encounter their cognate antigen, here presented by DCs, initiating commitment towards a T follicular helper (Tfh) cell phenotype [19]. Tfh cell commitment is accompanied by CCR7 down-regulation and CXCR5 upregulation, promoting Tfh cell migration to the T/B cell boundary where they can support B cell expansion [20,21].…”

Section: Gc Structure Formation and B Cell Movementmentioning

confidence: 99%

Transcription factors regulating B cell fate in the germinal centre

Recaldin

Fear

2015

Clinical and Experimental Immunology

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SummaryDiversification of the antibody repertoire is essential for the normal operation of the vertebrate adaptive immune system. Following antigen encounter, B cells are activated, proliferate rapidly and undergo two diversification events; somatic hypermutation (followed by selection), which enhances the affinity of the antibody for its cognate antigen, and classswitch recombination, which alters the effector functions of the antibody to adapt the response to the challenge faced. B cells must then differentiate into antibody-secreting plasma cells or long-lived memory B cells. These activities take place in specialized immunological environments called germinal centres, usually located in the secondary lymphoid organs. To complete the germinal centre activities successfully, a B cell adopts a transcriptional programme that allows it to migrate to specific sites within the germinal centre, proliferate, modify its DNA recombination and repair pathways, alter its apoptotic potential and finally undergo terminal differentiation. To co-ordinate these processes, B cells employ a number of 'master regulator' transcription factors which mediate wholesale transcriptomic changes. These master transcription factors are mutually antagonistic and form a complex regulatory network to maintain distinct gene expression programs. Within this network, multiple points of positive and negative feedback ensure the expression of the 'master regulators', augmented by a number of 'secondary' factors that reinforce these networks and sense the progress of the immune response. In this review we will discuss the different activities B cells must undertake to mount a successful T cell-dependent immune response and describe how a regulatory network of transcription factors controls these processes.

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Section: Gc Structure Formation and B Cell Movementmentioning

confidence: 99%

Transcription factors regulating B cell fate in the germinal centre

Recaldin

Fear

2015

Clinical and Experimental Immunology

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“…Interestingly, IRF4 binds to the Zbtb20 promoter and up-regulates Zbtb20 expression (37,38). Thus, LMP2A-and IRF4-mediated up-regulation of Zbtb20 may be an important mechanism by which EBV promotes plasma cell survival.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, LMP2A-and IRF4-mediated up-regulation of Zbtb20 may be an important mechanism by which EBV promotes plasma cell survival. Recent studies revealed that Zbtb20, which is a Bcl6 homolog and a member of the broad complex BTB zinc finger family, is a transcriptional repressor that has critical roles in plasma cell differentiation and survival (37,45). Zbtb20 is physiologically expressed in B1 and GC B cells, with highest expression in long-lived bone marrow ASCs (37).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies revealed that Zbtb20, which is a Bcl6 homolog and a member of the broad complex BTB zinc finger family, is a transcriptional repressor that has critical roles in plasma cell differentiation and survival (37,45). Zbtb20 is physiologically expressed in B1 and GC B cells, with highest expression in long-lived bone marrow ASCs (37). Zbtb20 enhances primary B-cell terminal differentiation into ASCs and enhances plasma cell survival in a B-cell-intrinsic manner (45).…”

Section: Discussionmentioning

confidence: 99%

“…5B). Zbtb20 encodes a zinc finger protein that has been shown to be important for B-cell differentiation into ASCs and for plasma cell longevity (37,38). Therefore, the induction of Zbtb20 expression by LMP2A in B cells may at contribute, at least in part, to the observed LMP2A effects on B-cell differentiation into antibody-secreting plasma cells.…”

Section: Lmp2a Expression In Gc B Cells Leads To Autoantibody Productionmentioning

confidence: 99%

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