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
Affiliations
Dana Piovesan
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
Jessica Tempany
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
Andrea Di Pietro
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
Inge Baas
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
Callisthenis Yiannis
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
Kristy O’Donnell
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Immunology and Pathology, Monash University, Prahan, VIC 3004, Australia
Yunshun Chen
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
Victor Peperzak
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
Gabrielle T. Belz
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
Charles R. Mackay
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
Gordon K. Smyth
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; The Department of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia
Joanna R. Groom
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
David M. Tarlinton
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Immunology and Pathology, Monash University, Prahan, VIC 3004, Australia
Kim L. Good-Jacobson
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Corresponding author
Summary: 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. : Piovesan et al. examine how B cells establish transcriptional programs that result in tailored responses to invading pathogens. The authors find that the transcription factor c-Myb represses the T-bet-mediated anti-viral program in B cells. c-Myb limits inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Keywords: B cells, c-Myb, T-bet, immunoglobulin, CXCR3, plasma cell, germinal center
