title: The nervous system as ectopic germinal center: CXCL13 and IgG in lyme neuroborreliosis.
abstract: Lyme neuroborreliosis (LNB) is a chronic infection in which B-cell activation, plasma cell infiltration, and enhanced Ig production in infected tissue are prominent feature. However, little is known about how B cells and plasma cells invade and persist in target organs. To assess this issue, we developed real-time PCR measurements of IgG and CXCL13 production. We used these RNA assays and specific enzyme-linked immunosorbent assays for protein and demonstrated that human peripheral blood mononuclear cells (PBMCs), stimulated by Borrelia burgdorferi sonicate, produced CXCL13 and IgG. Magnetic separation of PBMC populations and flow cytometry showed that CXCL13 is produced by dendritic cells. We then measure the expression of CXCL13 and IgG in tissues and correlated the expression of these host genes with spirochetal load. We also measured expression of dbpA and BBK32, two spirochetal genes important in chronic infection. There was a strong correlation between host immune response gene expression (CXCL13 and IgG) and spirochetal load. Immunohistochemistry of infected nonhuman primates tissue confirmed that CXCL13 is expressed in the nervous system. We conclude that persistent production of CXCL13 and IgG within infected tissue, two characteristics of ectopic germinal centers, are definitive features of LNB.
authors.affiliation: University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Narayan
authors.forename: Donna
authors.initials: D
authors.lastname: Dail
authors.forename: Libin
authors.initials: L
authors.lastname: Li
authors.forename: Diego
authors.initials: D
authors.lastname: Cadavid
authors.forename: Sheela
authors.initials: S
authors.lastname: Amrute
authors.forename: Patricia
authors.initials: P
authors.lastname: Fitzgerald-Bocarsly
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pachner
mesh_terms: D000818:Animals; D002460:Cell Line; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000382:microbiology; D020852:Lyme Neuroborreliosis / Q000276:immunology* / Q000503:physiopathology; D008253:Macaca mulatta; D008297:Male; D009420:Nervous System / Q000276:immunology* / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D007074:Immunoglobulin G