title: CXCR4/IgG-expressing plasma cells are associated with human gastrointestinal tissue inflammation.
abstract: BACKGROUND
  We previously reported abnormalities in circulating B cells in patients with chronic granulomatous disease (CGD) and those with HIV infection. Gastrointestinal complications are common to both diseases and likely involve perturbation of immune cells, including plasma cells (PCs). IgA is the most abundant immunoglobulin in the human body, with roles in protection and maintenance of intestinal homeostasis. IgA is produced primarily by PCs residing in mucosal tissues that are also thought to circulate in the blood.
  
  
  OBJECTIVE
  We sought to characterize and compare PCs in patients with infectious (HIV) and noninfectious (CGD and Crohn disease) diseases that have been associated with intestinal inflammation.
  
  
  METHODS
  Phenotypic and transcriptional analyses were performed on cells isolated from the blood and colon.
  
  
  RESULTS
  IgA-secreting CCR10-expressing PCs predominated in the guts of healthy subjects, whereas in patients with HIV, CGD, and Crohn disease, there was a significant increase in the proportion of IgG-secreting PCs. Where intestinal inflammation was present, IgG-secreting PCs expressed reduced levels of CCR10 and increased levels of CXCR4. The intensity of CXCR4 expression correlated with the frequency of IgG-expressing PCs and the frequency of CXCR4(+)/IgG(+) PCs was associated with the severity of intestinal inflammatory disease yet distinct from PCs and plasmablasts circulating in the blood.
  
  
  CONCLUSIONS
  These findings suggest that regardless of the underlying disease, the presence of CXCR4(+)/IgG(+) PCs in the gut is a strong yet localized indicator of intestinal inflammation. Furthermore, our findings suggest that CXCR4(+)/IgG(+) PCs might play a role in immune cell homeostasis during inflammatory processes of the gut.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Clarisa M
authors.initials: CM
authors.lastname: Buckner
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md. Electronic address: smoir@niaid.nih.gov.
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Lela
authors.initials: L
authors.lastname: Kardava
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Jason
authors.initials: J
authors.lastname: Ho
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Santich
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Leo Jin Young
authors.initials: LJ
authors.lastname: Kim
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Funk
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Nelson
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Britanny
authors.initials: B
authors.lastname: Winckler
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Chairez
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Narda L
authors.initials: NL
authors.lastname: Theobald-Whiting
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Sandra
authors.initials: S
authors.lastname: Anaya-O'Brien
authors.affiliation: Laboratory of Pathology, National Cancer Institute, Bethesda, Md.
authors.forename: Meghna
authors.initials: M
authors.lastname: Alimchandani
authors.affiliation: Laboratory of Pathology, National Cancer Institute, Bethesda, Md.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Quezado
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Yao
authors.affiliation: Critical Care Medicine, National Institutes of Health Clinical Center, Bethesda, Md.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Md. Electronic address: sderavin@niaid.nih.gov.
authors.forename: Suk See
authors.initials: SS
authors.lastname: De Ravin
mesh_terms: D000328:Adult; D001706:Biopsy; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D005260:Female; D005759:Gastroenteritis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D019718:Receptors, CXCR4; D016201:Receptors, Lymphocyte Homing
keywords: Plasma cells; gastrointestinal inflammation; homing receptors; inflammatory bowel disease; primary and infectious immunodeficiencies