title: Entry of Francisella tularensis into Murine B Cells: The Role of B Cell Receptors and Complement Receptors.
abstract: Francisella tularensis, the etiological agent of tularemia, is an intracellular pathogen that dominantly infects and proliferates inside phagocytic cells but can be seen also in non-phagocytic cells, including B cells. Although protective immunity is known to be almost exclusively associated with the type 1 pathway of cellular immunity, a significant role of B cells in immune responses already has been demonstrated. Whether their role is associated with antibody-dependent or antibody-independent B cell functions is not yet fully understood. The character of early events during B cell-pathogen interaction may determine the type of B cell response regulating the induction of adaptive immunity. We used fluorescence microscopy and flow cytometry to identify the basic requirements for the entry of F. tularensis into B cells within in vivo and in vitro infection models. Here, we present data showing that Francisella tularensis subsp. holarctica strain LVS significantly infects individual subsets of murine peritoneal B cells early after infection. Depending on a given B cell subset, uptake of Francisella into B cells is mediated by B cell receptors (BCRs) with or without complement receptor CR1/2. However, F. tularensis strain FSC200 ΔiglC and ΔftdsbA deletion mutants are defective in the ability to enter B cells. Once internalized into B cells, F. tularensis LVS intracellular trafficking occurs along the endosomal pathway, albeit without significant multiplication. The results strongly suggest that BCRs alone within the B-1a subset can ensure the internalization process while the BCRs on B-1b and B-2 cells need co-signaling from the co receptor containing CR1/2 to initiate F. tularensis engulfment. In this case, fluidity of the surface cell membrane is a prerequisite for the bacteria's internalization. The results substantially underline the functional heterogeneity of B cell subsets in relation to F. tularensis.
authors.affiliation: Department of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Plzakova
authors.affiliation: Department of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Krocova
authors.affiliation: Department of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Klara
authors.initials: K
authors.lastname: Kubelkova
authors.affiliation: Department of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Ales
authors.initials: A
authors.lastname: Macela
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000382:microbiology; D001692:Biological Transport; D002460:Cell Line; D005260:Female; D005604:Francisella tularensis / Q000502:physiology*; D005798:Genes, Bacterial; D054884:Host-Pathogen Interactions; D021962:Membrane Microdomains / Q000378:metabolism; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D017384:Sequence Deletion; D014406:Tularemia / Q000382:microbiology*
chemical_list: D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017452:Receptors, IgG