Journal
EBIOMEDICINE
Volume 24, Issue -, Pages 216-230Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.08.030
Keywords
Follicular helper T (Tfh) cells; Plasmodium; Vector transmission; Signaling Lymphocyte Activation Molecule (SLAM)-Associated Protein (SAP); GC B cells
Funding
- UK Medical Research Council [FC001101]
- Cancer Research UK [FC001101]
- Wellcome Trust [FC001101, WT101777MA]
- The Francis Crick Institute [10352, 10101] Funding Source: researchfish
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CD4(+) follicular helper T (Tfh) cells have been shown to be critical for the activation of germinal center (GC) B-cell responses. Similar to other infections, Plasmodium infection activates both GC as well as non-GC B cell responses. Here, we sought to explore whether Tfh cells and GC B cells are required to eliminate a Plasmodium infection. A CD4 T cell-targeted deletion of the gene that encodes Bcl6, the master transcription factor for the Tfh program, resulted in complete disruption of the Tfh response to Plasmodium chabaudi in C57BL/6mice and consequent disruption of GC responses and IgG responses and the inability to eliminate the otherwise self-resolving chronic P. chabaudi infection. On the other hand, and contrary to previous observations in immunization and viral infection models, Signaling Lymphocyte Activation Molecule (SLAM)-Associated Protein (SAP)-deficient mice were able to activate Tfh cells, GC B cells, and IgG responses to the parasite. This study demonstrates the critical role for Tfh cells in controlling this systemic infection, and highlights differences in the signals required to activate GC B cell responses to this complex parasite compared with those of protein immunizations and viral infections. Therefore, these data are highly pertinent for designing malaria vaccines able to activate broadly protective B-cell responses. (C) 2017 The Authors. Published by Elsevier B. V. This is an open access article under the CC BY license
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