{"doi":"10.3389/fcimb.2021.789373","title":"Trypanosoma cruzi Induces B Cells That Regulate the CD4+ T Cell Response","abstract":"Trypanosoma cruzi infection induces a polyclonal B cell proliferative response characterized by maturation to plasma cells, excessive generation of germinal centers, and secretion of parasite-unrelated antibodies. Although traditionally reduced to the humoral response, several infectious and non-infectious models revealed that B lymphocytes could regulate and play crucial roles in cellular responses. Here, we analyze the trypomastigote-induced effect on B cells, their effects on CD4 + T cells, and their correlation with in vivo findings. The trypomastigotes were able to induce the proliferation and the production of IL-10 or IL-6 of naïve B cells in co-culture experiments. Also, we found that IL-10-producing B220 lo cells were elicited in vivo . We also found up-regulated expression of FasL and PD-L1, proteins involved in apoptosis induction and inhibition of TCR signaling, and of BAFF and APRIL mRNAs, two B-cell growth factors. Interestingly, it was observed that IL-21, which plays a critical role in regulatory B cell differentiation, was significantly increased in B220 + /IL-21 + in in vivo infections. This is striking since the secretion of IL-21 is associated with T helper follicular cells. Furthermore, trypomastigote-stimulated B-cell conditioned medium dramatically reduced the proliferation and increased the apoptotic rate on CD3/CD28 activated CD4 + T cells, suggesting the development of effective regulatory B cells. In this condition, CD4 + T cells showed a marked decrease in proliferation and viability with marginal IL-2 or IFNγ secretion, which is counterproductive with an efficient immune response against T. cruzi . Altogether, our results show that B lymphocytes stimulated with trypomastigotes adopt a particular phenotype that exerts a strong regulation of this T cell compartment by inducing apoptosis, arresting cell division, and affecting the developing of a proinflammatory response.","journal":"Frontiers in Cellular and Infection Microbiology","year":2022,"id":266979,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":425179,"name":"Adriano Bertelli","orcid":null,"position":1,"is_corresponding":false},{"id":928107,"name":"Cecilia A. Pratto","orcid":null,"position":2,"is_corresponding":false},{"id":417460,"name":"Ramiro E. Verdún","orcid":"0000-0003-0530-4807","position":3,"is_corresponding":false},{"id":319764,"name":"Oscar Campetella","orcid":"0000-0002-7018-375X","position":4,"is_corresponding":false},{"id":319766,"name":"Juan Mucci","orcid":"0000-0002-7394-709X","position":5,"is_corresponding":false},{"id":928106,"name":"Martín Somoza","orcid":null,"position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:27:02.050512Z","pmid":"35071041","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}