Gamma 3 gene-disrupted mice selectively deficient in the dominant IgG subclass made to bacterial polysaccharides undergo normal isotype switching after immunization with polysaccharide-protein conjugate vaccines. J Immunol 1998 Oct 01;161(7):3393-9
Date
10/06/1998Pubmed ID
9759856Scopus ID
2-s2.0-0032193985 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Bacterial polysaccharides (PS) are T-independent type 2 Ags that elicit restricted Ab responses of IgM and IgG3 in mice and IgM and predominantly IgG2 in humans. Immunodeficiency in the dominant IgG subclass made to PS is associated with chronic sinus and pulmonary infections with PS-encapsulated bacteria. To elucidate the biologic role of the dominant IgG subclass in the immune response to PS and to make an animal model of human IgG subclass deficiency, we generated mice with a targeted disruption of the exon encoding the CH1 domain of the gamma 3 heavy-chain constant region gene. Homozygotes had no detectable serum IgG3, and their splenocytes did not produce IgG3 after LPS stimulation. IgG3(-/-) mice immunized with PS from Pseudomonas aeruginosa LPS O-side chain or Streptococcus pneumoniae type 19F capsule did not produce any IgG3 anti-PS Abs, in contrast to wild-type mice in which IgG3 was the major IgG subclass. Immunizing both wild-type and IgG3(-/-) mice with 19F PS-protein conjugate elicited IgG1 Abs. We conclude that IgG3(-/-) mice have a selective deficiency in the dominant murine IgG subclass made to T-independent type 2 Ags and may be a useful animal model of IgG subclass deficiency. In addition, we show that the anti-PS Ab class switching to IgG1 that occurs when mice are immunized with a PS-protein conjugate vaccine does not require sequential Ig expression or an intact, upstream gamma 3 heavy-chain gene.
Author List
Shapiro DA, Threadgill DS, Copfer MJ, Corey DA, McCool TL, McCormick LL, Magnuson TR, Greenspan NS, Schreiber JRMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies, Bacterial
Bacterial Vaccines
Cells, Cultured
Crosses, Genetic
Female
Genes, Immunoglobulin
IgG Deficiency
Immunoglobulin Class Switching
Immunoglobulin G
Immunoglobulin Heavy Chains
Lipopolysaccharides
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Molecular Weight
Polysaccharides, Bacterial
Pseudomonas aeruginosa
Recombination, Genetic
Spleen
Vaccines, Conjugate
