Projects per year
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 language | English |
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Pages (from-to) | 461-470 |
Number of pages | 10 |
Journal | Cell Reports |
Volume | 19 |
Issue number | 3 |
DOIs | |
Publication status | Published - 18 Apr 2017 |
Keywords
- B cells
- c-Myb
- CXCR3
- germinal center
- immunoglobulin
- plasma cell
- T-bet
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NHMRC Principal Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
11/01/16 → 31/12/19
Project: Research
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How the immune system responds to different types of infection and establishes immunity
Jacobson, K. & Groom, J.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 31/01/18
Project: Research
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A Systems Approach to the Adaptive Immune Response
Hodgkin, P. D., Corcoran, L. M., Tarlinton, D., Belz, G. T. & Nutt, S. L.
1/01/14 → 31/12/18
Project: Research