title: B cell-deficient mice are highly resistant to Leishmania donovani infection, but develop neutrophil-mediated tissue pathology.
abstract: Resolution of Leishmania infection is T cell-dependent, and B lymphocytes have been considered to play a minimal role in host defense. In this study, the contribution of B lymphocytes to the response against Leishmania donovani was investigated using genetically modified IgM transmembrane domain (muMT) mutant mice, which lack mature B lymphocytes. When compared with wild-type mice, muMT mice cleared parasites more rapidly from the liver, and infection failed to establish in the spleen. The rapid clearance of parasites in muMT mice was associated with accelerated and more extensive hepatic granuloma formation compared with wild-type mice. However, the liver of infected muMT mice also showed signs of destructive pathology, associated with the presence of increased numbers of neutrophils. The role of neutrophils in controlling parasite growth in the viscera was determined by depletion with the mAb RB6-8C5. This treatment led to a dramatic enhancement of parasite growth in both the liver and spleen of muMT and wild-type mice. As assessed by transfer of both normal and chronic-infection serum, Ig protects microMT mice from destructive hepatic pathology, but minimally alters their resistance compared with wild-type mice. However, adoptive transfer of CD4+ and CD8+ T cells into recombinase activating gene 1 (RAG1-/-) recipients, suggested that T cell function was not altered by maturation in a B cell-deficient environment. Taken together, these data suggest an inhibitory role for B lymphocytes in resistance to L. donovani unrelated to the presence or absence of Ig. However, Ig protects muMT mice from the exaggerated pathology that occurs during infection.
authors.affiliation: Department of Infectious Diseases, London School of Hygiene and Tropical Medicine, London United Kingdom.
authors.forename: S C
authors.initials: SC
authors.lastname: Smelt
authors.forename: S E
authors.initials: SE
authors.lastname: Cotterell
authors.forename: C R
authors.initials: CR
authors.lastname: Engwerda
authors.forename: P M
authors.initials: PM
authors.lastname: Kaye
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007116:Immunization, Passive; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D007958:Leukocyte Count; D008099:Liver / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009503:Neutropenia / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000469:parasitology / Q000637:transplantation
chemical_list: D007148:Immunoglobulin mu-Chains