Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 214, Issue 9, Pages 2795-2810Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161955
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Funding
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Uehara Memorial Foundation
- National Cancer Institute, National Institutes of Health
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T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7-and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7-and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity.
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