c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses
| Autor: | Charles R. Mackay, David M. Tarlinton, Inge Baas, Dana Piovesan, Andrea Di Pietro, Yunshun Chen, Kristy O'Donnell, Jessica C Tempany, Victor Peperzak, Gordon K. Smyth, Kim L. Good-Jacobson, Gabrielle T. Belz, Callisthenis Yiannis, Joanna R Groom |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Receptors CXCR3 Transcription Genetic Cellular differentiation Plasma Cells Antibody Affinity chemical and pharmacologic phenomena Plasma cell Biology General Biochemistry Genetics and Molecular Biology Mice Proto-Oncogene Proteins c-myb 03 medical and health sciences 0302 clinical medicine Plasma cell differentiation medicine Animals Humans lcsh:QH301-705.5 Transcription factor Regulation of gene expression B-Lymphocytes CD40 Germinal center Cell Differentiation Germinal Center 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation lcsh:Biology (General) Antibody Formation Immunology biology.protein Female Syndecan-1 T-Box Domain Proteins Gene Deletion 030215 immunology |
| Zdroj: | Cell Reports, Vol 19, Iss 3, Pp 461-470 (2017) |
| ISSN: | 2211-1247 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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