FDCs are stromal cell of the lymphoid organs that play a central role in the induction of humoral immune response. FDCs deliver signal to B cells by trapping intact antigen onto their surface as antigen-antibodies or antigen-complement fragments immune complexes. Thus cognate B cells recognize the antigen presented by FDCs via BCR, while surface proteins or soluble factors expressed by FDCs serve as co-stimulation. FDC activation is pivotal for the origin of germinal center (GC) reaction, and TLR4 engagement appears critical for this purpose. Nevertheless, no studies analyzing the commitment of FDC during vaccination with licensed adjuvants have been performed. Here we show for the first time, that the intramuscular injection of adjuvants approved for human use leads to FDC activation, which occurs late after injection. In addition, we observe that the activation of FDCs upon injection of an adjuvanted antigen takes place only in the follicles where a GC reaction occurs and the number of follicles with activated FDCs strictly correlates with the antigen-specific antibody titers. Moreover, retention of the injected antigen is observed only in the follicles that contain activated FDCs. Thus the extent of the humoral immune response against an antigen correlates with the activation state of FDCs, which can be modulated by the presence of the adjuvants, maybe through an indirect effect. The elucidation of the adjuvant affect on FDCs can help to design more efficacious vaccines.
- Copyright © 2011 by The American Association of Immunologists, Inc.