title: B cell: T cell interactions occur within hepatic granulomas during experimental visceral leishmaniasis.
abstract: Hepatic resistance to Leishmania donovani infection in mice is associated with the development of granulomas, in which a variety of lymphoid and non-lymphoid populations accumulate. Although previous studies have identified B cells in hepatic granulomas and functional studies in B cell-deficient mice have suggested a role for B cells in the control of experimental visceral leishmaniasis, little is known about the behaviour of B cells in the granuloma microenvironment. Here, we first compared the hepatic B cell population in infected mice, where ≈60% of B cells are located within granulomas, with that of naïve mice. In infected mice, there was a small increase in mIgM(lo)mIgD(+) mature B2 cells, but no enrichment of B cells with regulatory phenotype or function compared to the naïve hepatic B cell population, as assessed by CD1d and CD5 expression and by IL-10 production. Using 2-photon microscopy to quantify the entire intra-granuloma B cell population, in conjunction with the adoptive transfer of polyclonal and HEL-specific BCR-transgenic B cells isolated from L. donovani-infected mice, we demonstrated that B cells accumulate in granulomas over time in an antigen-independent manner. Intra-vital dynamic imaging was used to demonstrate that within the polyclonal B cell population obtained from L. donovani-infected mice, the frequency of B cells that made multiple long contacts with endogenous T cells was greater than that observed using HEL-specific B cells obtained from the same inflammatory environment. These data indicate, therefore, that a subset of this polyclonal B cell population is capable of making cognate interactions with T cells within this unique environment, and provide the first insights into the dynamics of B cells within an inflammatory site.
authors.affiliation: Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, Heslington, York, United Kingdom.
authors.forename: John W J
authors.initials: JW
authors.lastname: Moore
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dalton
authors.forename: Benjamin M J
authors.initials: BM
authors.lastname: Owens
authors.forename: Asher
authors.initials: A
authors.lastname: Maroof
authors.forename: Mark C
authors.initials: MC
authors.lastname: Coles
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D055610:Antigens, CD1d / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology*; D018956:CD5 Antigens / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D006099:Granuloma / Q000469:parasitology* / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000378:metabolism*; D008099:Liver / Q000469:parasitology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D055610:Antigens, CD1d; D018956:CD5 Antigens; D016753:Interleukin-10