Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

Blood. 2012 Dec 6;120(24):4850-8. doi: 10.1182/blood-2012-05-430959. Epub 2012 Oct 16.

Abstract

CD27(+) memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27(+) but also IgG(+) B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG(+) B cells, the ratio of CD27(-) to CD27(+) was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27(-)IgG(+) B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27(+) counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27(-)IgG(+) B-cell compartment. Together, these findings show that, despite reduced circulating CD27(+) memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27(-) B cells.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Enzyme-Linked Immunospot Assay
  • Female
  • Flow Cytometry
  • Granulomatous Disease, Chronic / blood
  • Granulomatous Disease, Chronic / genetics
  • Granulomatous Disease, Chronic / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulin kappa-Chains / immunology
  • Immunoglobulin lambda-Chains / genetics
  • Immunoglobulin lambda-Chains / immunology
  • Immunologic Memory / genetics
  • Immunologic Memory / immunology*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mutation
  • NADPH Oxidase 2
  • NADPH Oxidases / genetics
  • NADPH Oxidases / immunology
  • Somatic Hypermutation, Immunoglobulin
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / blood
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology*
  • Young Adult

Substances

  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Membrane Glycoproteins
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases
  • neutrophil cytosolic factor 1