Gamma 3 gene-disrupted mice selectively deficient in the dominant IgG subclass made to bacterial polysaccharides. II. Increased susceptibility to fatal pneumococcal sepsis due to absence of anti-polysaccharide IgG3 is corrected by induction of anti-polysaccharide IgG1

The Journal of Immunology : Official Journal of the American Association of Immunologists
John McLayJohn R Schreiber

Abstract

Bacterial polysaccharides (PS) are type 2 T-independent Ags that elicit Abs restricted in isotype to IgM and predominantly IgG2 in humans and IgM, and IgG3 in mice. Humans with IgG2 subclass deficiency are susceptible to sinus and pulmonary infections with PS-encapsulated bacteria. We previously developed an IgG3-deficient mouse by disrupting the gamma3 H chain constant region gene via targeted mutagenesis. Mutant mice lacking IgG3 were backcrossed for 10 generations to wild-type (WT) BALB/c mice to generate BALB/c mice that have complete absence of IgG3. WT mice immunized with type 3 Streptococcus pneumoniae capsular PS made anti-PS IgM, IgG3, and small quantities of IgG1, which opsonized S. pneumoniae for killing by polymorphonuclear leukocytes. These mice were protected against death from lethal doses of type 3 S. pneumoniae. In contrast, IgG3(-/-) mice made similar titers of anti-PS IgM and IgG1 as WT mice but no IgG3, and had poorly opsonic sera with significantly increased mortality after S. pneumoniae challenge. Immunization of IgG3(-/-) mice with type 3 S. pneumoniae PS conjugated to carrier protein CRM(197)-elicited IgM and high-titer IgG1 Abs, restored serum opsonization, and gave protection from mortality after S. pn...Continue Reading

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Citations

May 7, 2003·The Journal of Experimental Medicine·Teresita Díaz de StåhlBirgitta Heyman
Jun 25, 2003·Current Opinion in Infectious Diseases·Julio Casal, David Tarragó
Jan 28, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jerome T McKayKaren M Haas
May 11, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kalgi D PandyaKishore R Alugupalli
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Girish S KirimanjeswaraEric T Harvill
Feb 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa J KobrynskiFrancis K Lee
Nov 25, 2005·Scandinavian Journal of Immunology·F HjelmB Heyman
Jul 13, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lu ZhangBirgitta Heyman
Nov 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Niansheng ChuLaurence U Buxbaum
May 28, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne K ShrinerKishore R Alugupalli
Jul 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·P'ng LokeJames P Allison
Nov 19, 2013·European Journal of Immunology·Branislav KrljanacFalk Weih
Jul 9, 2014·Molecular Immunology·Anna SörmanBirgitta Heyman

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