In previous studies, we identified a gene product belonging to the silent information regulatory 2 protein (SIR2) family. This protein is expressed by all Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L. mexicana) and found to be crucial for parasite survival and virulence. In the present study, we investigated whether a Leishmania SIR2 recombinant protein (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased expression of CD69 on B cells. This effect was not abolished by the addition of polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased spleen B cell number by a factor of about approximately 1.6, whereas no modification occurred at the level of CD4(+) and CD8(+) cells. Furthermore, intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or nude mice triggered the production of elevated levels of LmSIR2-specific antibodies. The analysis of specific isotype profiles showed a predominance of immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of complement induced the in vitro lysis of L. infantum amastigotes. In the absence of complement, the antibodies induced significant inhibition of amastigotes developpement inside macrophages. Together, the current study provides the first evidence that a Leishmania protein belonging to the SIR2 family may play a role in the regulation of immune response through its capacity to trigger B-cell effector function.