Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells.
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.
Laboratories of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes ofHealth, Bethesda, MD 20892, USA, smoir@niaid.nih.gov
Susan
S
Moir
Suk See
SS
De Ravin
Brian H
BH
Santich
Jin Young
JY
Kim
Jacqueline G
JG
Posada
Jason
J
Ho
Clarisa M
CM
Buckner
Wei
W
Wang
Lela
L
Kardava
Mary
M
Garofalo
Beatriz E
BE
Marciano
Jody
J
Manischewitz
Lisa R
LR
King
Surender
S
Khurana
Tae-Wook
TW
Chun
Hana
H
Golding
Anthony S
AS
Fauci
Harry L
HL
Malech
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000276:immunology*; D055815:Young Adult
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D008562:Membrane Glycoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1