c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses

Dana Piovesan, Jessica Tempany, Andrea Di Pietro, Inge Baas, Callisthenis Yiannis, Kristy O'Donnell, Yunshun Chen, Victor Peperzak, Gabrielle T Belz, Charles R. Mackay, Gordon K Smyth, Joanna R Groom, David M. Tarlinton, Kim L. Good-Jacobson

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders.

Original languageEnglish
Pages (from-to)461-470
Number of pages10
JournalCell Reports
Volume19
Issue number3
DOIs
Publication statusPublished - 18 Apr 2017

Keywords

  • B cells
  • c-Myb
  • CXCR3
  • germinal center
  • immunoglobulin
  • plasma cell
  • T-bet

Cite this

Piovesan, Dana ; Tempany, Jessica ; Di Pietro, Andrea ; Baas, Inge ; Yiannis, Callisthenis ; O'Donnell, Kristy ; Chen, Yunshun ; Peperzak, Victor ; Belz, Gabrielle T ; Mackay, Charles R. ; Smyth, Gordon K ; Groom, Joanna R ; Tarlinton, David M. ; Good-Jacobson, Kim L. / c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses. In: Cell Reports. 2017 ; Vol. 19, No. 3. pp. 461-470.
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Piovesan, D, Tempany, J, Di Pietro, A, Baas, I, Yiannis, C, O'Donnell, K, Chen, Y, Peperzak, V, Belz, GT, Mackay, CR, Smyth, GK, Groom, JR, Tarlinton, DM & Good-Jacobson, KL 2017, 'c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses', Cell Reports, vol. 19, no. 3, pp. 461-470. https://doi.org/10.1016/j.celrep.2017.03.060

c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses. / Piovesan, Dana; Tempany, Jessica; Di Pietro, Andrea; Baas, Inge; Yiannis, Callisthenis; O'Donnell, Kristy; Chen, Yunshun; Peperzak, Victor; Belz, Gabrielle T; Mackay, Charles R.; Smyth, Gordon K; Groom, Joanna R; Tarlinton, David M.; Good-Jacobson, Kim L.

In: Cell Reports, Vol. 19, No. 3, 18.04.2017, p. 461-470.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Belz, Gabrielle T

AU - Mackay, Charles R.

AU - Smyth, Gordon K

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N2 - Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders.

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