Functional properties of isotype-switched immunoglobulin M (IgM) and IgG monoclonal antibodies to Pseudomonas aeruginosa lipopolysaccharide.
Controversy exists regarding isotype-related differences in the antibacterial and protective properties of lipopolysaccharide (LPS)-specific antibodies of the immunoglobulin M (IgM) class and various IgG subclasses. To clarify this issue, a murine hybridoma secreting IgM monoclonal antibody (MAb) specific for the O polysaccharide of Pseudomonas aeruginosa serogroup O6 LPS was class switched, by sib selection, to produce an IgG3 MAb with identical specificity and variable region heavy and light chain nucleotide sequences. This IgG3-secreting cell line was further switched to the production of O-specific, variable region-identical IgG1, IgG2b, and IgG2a MAbs. Functional comparisons of these LPS-specific IgM and IgG MAb isotypes revealed similar LPS binding, opsonic, and protective activities. Relatively minor isotype-related differences in levels of efficiency of MAb-mediated, complement-dependent opsonophagocytic killing (IgM > IgG2a > IgG3 > IgG2b > > IgG1) were not associated with corresponding differences in in vivo functions. These findings, in conjunction with previously published data, support a cautious approach to generic conclusions regarding the immunotherapeutic superiority of LPS-specific antibodies belonging to either the IgM or IgG class or to a particular IgG subclass.
Pollack
M
M
Department of Medicine, Uniformed Services, University of the Health Science, F. Edward Hébert School of Medicine, Bethesda, Maryland, USA.
Koles
N L
NL
Preston
M J
MJ
Brown
B J
BJ
Pier
G B
GB
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D001770:Blood Bactericidal Activity; D002056:Burns / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D007075:Immunoglobulin M / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009895:Opsonin Proteins; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D017931:DNA Primers; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D008070:Lipopolysaccharides; D009895:Opsonin Proteins