Noteworthy, Hsp90 has also been found to have a specific function in immunological processes. An increasing body of data suggests that certain Hsp90s play a role in both innate and adaptive immunity, and in some cases, the adjuvant effect of Hsp90s have been assessed . Hsp90s can elicit potent specific cellular adaptive order LDK378 immune responses based on their ability to Lapatinib EGFR/HER2 inhibitor chaperone antigenic peptides, and also act independently of chaperoned peptides to directly stimulate innate immune responses . Given the ancient origin of Hsp90s, such specialization may have occurred early in evolution and, therefore, it is feasible that these immunological properties of Hsp90 from humans and other organisms like bacteria and parasites are also present in their plant orthologs. In fact, plant Hsp90s are able to interact with animal co-chaperones and cooperate with them in the folding process, suggesting plasticity between chaperone complexes from different eukaryotic organisms . An open question is whether plant Hsp90s also present immunostimulatory properties as those observed in animal and protozoan Hsp90s. This is of importance because plants are considered novel bioreactors to produce pharmaceutical and vaccine molecules . However, since the production of high amounts of antigen in plants is generally difficult, there is a need to develop different strategies . An interesting option is to express the polypeptide of interest in plants with a carrier that could provide stability and therefore increase the polypeptide production . Should Hsp90s from plants present adjuvant properties, they could arise as novel and interesting carriers for proteins or peptides of immunoprotective value, improving the immunogenicity property of the transgenic plant extract. In the present work, we evaluated the ability of recombinant Nicotiana benthamiana and Arabidopsis thaliana Hsp90s to induce in vitro proliferation of splenocytes from na?��ve BALB/c, C3H/HeN and C3H/HeJ mice. In addition, we determined which subpopulations of spleen cells were stimulated by recombinant plant Hsp90s using flow cytometry. Our data indicate that their proliferative capacity is related to the fact that plant Hsp90s behave as potent B-cell mitogens. On the other hand, we showed by immunofluorescence analysis that rAtHsp81.2 co-localizes with anti-CD19 but not with anti-CD3 labeling, suggesting that rAtHsp81.2 interacts specifically with B-cells on their surface.