title: The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes.
abstract: The rate of pathogen clearance is a critical determinant of morbidity and mortality. We sought to characterize the immune response responsible for the remarkably rapid clearance of individual episodes of bacteremia caused by the relapsing fever bacterium, Borrelia hermsii. SCID or Rag(-/-) mice were incapable of resolving B. hermsii infection, indicating a critical role for T and/or B cells. TCR(-/-) mice, which lack T cells, and IL-7(-/-) mice, which are deficient in both T cells and follicular B cells, but not in B1 cells and splenic marginal zone (MZ) B cells, efficiently cleared B. hermsii. These findings suggested that B1 cells and/or MZ B cells, two B cell subsets that are known to participate in rapid, T-independent responses, might be involved. The efficient resolution of the episodes of moderate level bacteremia by splenectomized mice suggested that MZ B cells do not play the primary role in clearance of this bacterium. In contrast, xid mice, which are deficient in B1 cells, suffered more severe episodes of bacteremia than wild-type mice. The hypothesis that B1 cells are critical for clearance of B. hermsii was further supported by a selective expansion of the B1b (i.e., IgM(high), IgD(-/low), Mac1(+) CD23(-), and CD5(-)) cell subset in infected xid mice, which coincided with the eventual resolution of infection. Finally, mice selectively incapable of secreting IgM, the dominant isotype produced by B1 cells, were completely unable to clear B. hermsii. Together these results support the model that B1b cells generate the T-independent IgM required for the control and resolution of relapsing fever borreliosis.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA. kishore.alugupalli@umassmed.edu
authors.forename: Kishore R
authors.initials: KR
authors.lastname: Alugupalli
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gerstein
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Eva
authors.initials: E
authors.lastname: Szomolanyi-Tsuda
authors.forename: Robert T
authors.initials: RT
authors.lastname: Woodland
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D001770:Blood Bactericidal Activity / Q000235:genetics / Q000276:immunology; D001898:Borrelia / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D012061:Relapsing Fever / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology
chemical_list: D007075:Immunoglobulin M; C033027:secretory IgM