title: Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity.
abstract: Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and represents the most common infectious myocarditis worldwide. Autoimmunity is one of the mechanisms contributing to its pathogenesis. Although the cellular interactions that promote this autoimmune response are still poorly understood, several studies have demonstrated a key role for B lymphocytes since they secrete antibodies, cytokines and present antigens. Recently, we reported that immunization with cruzipain, an immunodominant T. cruzi antigen, induces a higher activation state in B cells from BALB/c mice (susceptible to cardiac autoimmunity) than B lymphocytes from C57BL/6 (a resistant strain). Here, we focused on the study of B cell survival in both mouse strains after cruzipain immunization and demonstrated an increased survival rate of B cells from BALB/c compared to C57BL/6 mice. This phenomenon was associated with a decreased expression of Fas/FasL and an increased expression of anti-apoptotic Bcl-2/Bcl-xL proteins. With the purpose to gain more knowledge about the mechanisms involved, we found that IL-4 produced by BALB/c B cells played a key role in the survival in an autocrine way whereas the addition of this bioactive cytokine rescued C57BL/6 B lymphocytes from apoptosis. Our findings suggest that in the absence of infection, both enhanced B cell activation induced by the immunization with a single parasite antigen and insufficient negative regulation can potentially contribute to autoimmunity seen in cruzipain immune BALB/c mice.
authors: Inmunología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, CIBICI-CONICET, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la Torre y Medina Allende S/N, 5000 Córdoba, Argentina. apellegrini@fcq.unc.edu.ar
authors: Andrea
authors: A
authors: Pellegrini
authors: Eugenio Antonio
authors: EA
authors: Carrera-Silva
authors: Alfredo
authors: A
authors: Arocena
authors: Roxana Carolina
authors: RC
authors: Cano
authors: Maria Pilar
authors: MP
authors: Aoki
authors: Susana
authors: S
authors: Gea
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D024722:Cardiac Myosins / Q000276:immunology; D002470:Cell Survival; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2; D015800:Protozoan Proteins; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity; D014611:Vaccination; D051020:bcl-X Protein / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D001323:Autoantibodies; C494812:Bcl2l1 protein, mouse; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015800:Protozoan Proteins; D051020:bcl-X Protein; D019014:fas Receptor; C052617:Bcl2 protein, mouse; D015847:Interleukin-4; D003546:Cysteine Endopeptidases; C063214:cruzipain; D024722:Cardiac Myosins