Bone marrow myeloid cells from Trypanosoma cruzi infected mice kill immature B cells through a mechanism involving prostaglandin-E2. EV Acosta Rodríguez, EI Zúñiga, MC Merino, CL Montes y A Gruppi. Inmunología. Facultad Ciencias Químicas. UNC. agruppi@bioclin.fcq.unc.edu.ar

A deficient humoral immune response may be originated at different levels of B cell development and, in case of infections, could have strong consequences in the control of microorganism replication and pathology development. We investigate the influence of T cruzi infection on the central B cell compartment. Mice ongoing the acute phase of the infection present a marked cellular hypoplasia in bone marrow (BM), which mainly affects immature B220^lowHSA^high B (imB) cells. This BM hypoplasia is not due to an enhanced migration to periphery since splenic imB cells are also reduced, but it could be a consequence of the increased apoptosis observed in the imB cell population. Even tough BM hypoplasia is transient and coincident with the presence of parasite in blood; apoptosis is not a direct effect of parasite-cell interaction, since T. cruzi trypomastigotes incubated with normal BM cells do not induce imm B cell elimination. By co-cultures, we demonstrated that infected mice BM cells secrete a soluble factor that kills imB cells. This factor is not IFN-g, TNF-a, TGF-b nor H₂O₂ but it is a product of the ciclooxigenase (COX) pathway since indomethacin treatment restrains the apoptosis observed. Furthermore, infected mice BM lose their killing activity when depleted from Mac+, but not Thy1.2+, cells. This effect is directly related to PGE2 level that is high in undepleted or Thy⁺-depleted infected mice BM but reduced after Mac⁺ cells depletion. Our findings indicate that T. cruzi infection induces myeloid cells to secrete PGE2 that eliminates imB cells. This event would affect the progression of the humoral by reducing the development of Ab-secreting cells and allowing an uncontrolled parasite replication