Activity of human IgG and IgA subclasses in immune defense against Neisseria meningitidis serogroup B.
Both IgG and IgA Abs have been implicated in host defense against bacterial infections, although their relative contributions remain unclear. We generated a unique panel of human chimeric Abs of all human IgG and IgA subclasses with identical V genes against porin A, a major subcapsular protein Ag of Neisseria meningitidis and a vaccine candidate. Chimeric Abs were produced in baby hamster kidney cells, and IgA-producing clones were cotransfected with human J chain and/or human secretory component. Although IgG (isotypes IgG1-3) mediated efficient complement-dependent lysis, IgA was unable to. However, IgA proved equally active to IgG in stimulating polymorphonuclear leukocyte respiratory burst. Remarkably, although porin-specific monomeric, dimeric, and polymeric IgA triggered efficient phagocytosis, secretory IgA did not. These studies reveal unique and nonoverlapping roles for IgG and IgA Abs in defense against meningococcal infections.
Vidarsson
G
G
Department of Immunology, Medarex Europe, Genmab, and Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, University Medical Center Utrecht, Utrecht, The Netherlands.
van Der Pol
W L
WL
van Den Elsen
J M
JM
Vilé
H
H
Jansen
M
M
Duijs
J
J
Morton
H C
HC
Boel
E
E
Daha
M R
MR
Corthésy
B
B
van De Winkel
J G
JG
D000818:Animals; D001433:Bacteriolysis / Q000235:genetics / Q000276:immunology; D001666:Binding Sites, Antibody / Q000235:genetics; D001770:Blood Bactericidal Activity / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003167:Complement Activation / Q000276:immunology; D006224:Cricetinae; D019281:Dimerization; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009345:Neisseria meningitidis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D018272:Porins / Q000276:immunology; D011961:Receptors, Fc / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology
C045281:IgA receptor; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D018272:Porins; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C034639:polymeric IgA; C057699:porin protein, Neisseria