Affiliation:
1. *Pediatrics and
2. ‡Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106
3. †Genetics, and
Abstract
AbstractBacterial 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 γ3 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 γ3 heavy-chain gene.
Publisher
The American Association of Immunologists
Subject
Immunology,Immunology and Allergy
Reference46 articles.
1. Sarvas, H. O., L. M. Aaltonen, F. Péterfy, I. J. T. Seppälä, O. Mäkelä. 1983. IgG subclass distributions in anti-hapten and anti-polysaccharide antibodies induced by haptenated polysaccharides. Eur. J. Immunol. 13: 409
2. Perlmutter, R. M., D. Hansburg, D. E. Briles, R. A. Nicolotti, J. M. Davie. 1978. Subclass restriction of murine anti-carbohydrate antibodies. J. Immunol. 121: 566
3. Yount, W. J., M. M. Dorner, H. G. Kunkel, E. A. Kabat. 1968. Studies on human antibodies. J. Exp. Med. 127: 633
4. Kuijpers, T. W., R. S. Weening, T. A. Out. 1992. IgG subclass deficiencies and recurrent pyogenic infections, unresponsiveness against bacterial polysaccharide antigens. Allergol. Immunopathol. 20: 28
5. Shackelford, P. G., S. J. Nelson, A. T. Palma, M. H. Nahm. 1988. Human antibodies to group A streptococcal carbohydrate: ontogeny, subclass restriction, and clonal diversity. J. Immunol. 140: 3200