Role of BAFF in the development of specific and autoreactive humoral response during Trypanosoma cruzi infection

BERMEJO D; GRUPPI A

Buenos Aires

Congreso; 3 Congreso Latinoamericano de Autoinmunidad; 2010

B cells and antibodies (Abs) are involved not only in controlling the spreading of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas' disease. Mice infected with T. cruzi develop splenomegaly showing massive and persistent germinal center and extrafollicular reactions and peritoneal B cell decrease associated to B cell differentiation, which are accompanied with high levels of parasite-specific and autoreactive Abs. Humoral response during T. cruzi infection showed a striking compartmentalization with peritoneum and lymph node cells producing higher amounts of Abs than spleen and BM cells. The changes in B cell compartment coincide with an increase in the concentration of BAFF, a cytokine involved in peripheral B cell survival and associated to autoimmunity. The role of BAFF in the development of B cell responses during experimental Chagas' disease was analyzed in BALB/c mice infected with 500 tripomastigotes which were injected i.p. with BR3:Fc to block BAFF activity. BAFF blockade decreased the number of mature but not immature B cells from spleen and lymph node. The number and proportion of B cells from bone marrow and peritoneum was not affected by the treatment. However, BR3:Fc treated infected mice showed a reduction of total IgM and IgG-isotypes in all the lymphoid tissues studied. BAFF blockade was effective to reduce the titers of Anti-nuclear IgG (ANA) and the titers of T. cruzi specific-IgM, but did not affect the titers of parasite-specific IgG or parasitema, but favors parasite replication in heart. Together, our results demonstrate a massive B cell response in T. cruzi infected mice which is partially mediated by BAFF, and shows for first time an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.