Leprosy is a still a serious human health problema in developed countries. Environmental and genetic factors are playing a key role in the chronic course of the disease, resistance versus susceptibility.  The multidrug treatment is not effective for all infected individuals; “cured” individuals mostly show relapses of neurological disordes and potential as the same as not cured can present physical and deformed constrainst.  The unsolved puzzle in leprosy is that clinic spectrum depends of the host immune response.and thus, the outcome of the immune response. In the present review we intended to describe some aspects of the immunotherapy, based on  type I IFNs and M. bovis BCG vaccine as a strategy such as sword to target germinal centers, either for the generation or for the enhancement and thus, throughout key signals delivered by folicular CD4+ T cells, and controlled by folicular regulatory CD4+ T cells, B cell differentiation into plasmacytoid cells be highly promoted the induction of protective high affinity neutralyzing antibodies to unlock  humoral immunity, protective toward M. leprae infected individuals.

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