BALB/c mice infected with T. cruzi develop splenomegaly with a massive and persistent germinal center and extrafollicular antibody (Ab) responses accompanied by high levels of parasite-specific and autoreactive Abs. The changes in spleen are associated with increased level of Baff (B cell activating factor belonging to the TNF family), a cytokine involved in peripheral B cell survival whose overexpression is associated with autoimmunity.
To analyze the potential role of Baff in the development of B cell response during experimental Chagas’ disease, BALB/c mice infected with 500 tripomastigotes were injected i.p. with 150 ug of BR3-Fc to block Baff activity or control mIgG2a Ab or PBS three times per week, starting in day 1 pi. We observed that blocking Baff decreases the % of splenic and lymph node B cells but not those one in bone marrow and peritoneum. In spleen, the most affected B cells are the mature one and, instead of B cell dropping off, proportionally plasma cells are increased. Interestingly Ab production is compartmentalized in T. cruzi infected mice with huge production in peritoneum and lymph nodes, but blocking Baff reduces total IgM and all IgG isotypes production in all tissues studied. Blockade of Baff activity affects T. cruzi specific-IgM but not -IgG production, and the control of parasite spreading is not affected by the treatment since the levels of parasitemia are similar in all infected mice. Anti-nuclear Ab-specific IgG decreased in BR3-Fc treated-infected mice. To sum up in T. cruzi infected mice Baff is controlling the development of autoreactive response and the T-independent parasite specific IgM response but not parasite replication.
