P3 mAb: An immunogenic anti-NeuGcGM3 antibody with unusual immunoregulatory properties

P3 is a murine IgM mAb that recognize N-glycosylated gangliosides, sulfatides, and anti- gens expressed in melanoma, breast, and lung human tumors.This antibody has the ability to trigger an IgG antibody response in the syngeneic BALB/c model, even when it is admin- istered in the absence of adjuvant or carrier protein.The mechanism by which the P3 mAb, a self-immunoglobulin, induce this immune response in the absence of co-stimulatory or classical danger signals is still unknown. In the present paper we show that the high immunogenicity of P3 mAb depends not only on CD4 but also on CD8⁺ T cells, since the depletion of CD8⁺ or CD4⁺ T cells led to the loss of P3 mAb immunogenicity in the syngeneic model. Furthermore, the immunization with P3 mAb enhanced the recovery of the CD8⁺ T cell population in mice treated with an anti-CD8a antibody. Additionally, the immunization with P3 mAb restored the capacity of immunosuppressed mice to reject allogeneic tumors, a mechanism mediated by the action of CD8⁺ T cells. Finally, in mice with cyclophosphamide induced lymphopenia, the administration of P3 mAb accelerated the recovery of both CD4⁺ and CD8⁺ T cells. These results show new possibilities for B and CD8⁺ T cells interactions during the immune response elicited by a self-protein. Fur- thermore they point to P3 mAb as a potential interesting candidate for the treatment of immunosuppressed patients.