MCLAY JM, PETERSON S, LEONARD E, SHAPIRO D, GREENSPAN N, SCHREIBER J; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. B-982.
Case Western Reserve University, Cleveland, OH
BACKGROUND: Bacterial PS are T independent antigens that elicit antibodies (Ab) restricted in IgG subclass and delayed in ontogeny. Humans with IgG2 deficiency, the dominant human anti-PS subclass, are susceptible to infections with encapsulated bacteria. In order to determine the pathophysiology of this increased susceptibility we developed a mouse deficient in the dominant anti-PS IgG subclass IgG3, the immunological equivalent of human IgG2. METHODS: We disrupted 54bp of the g3 heavy chain constant region gene via targeted mutagenesis and homologous recombination to make knockout mutant mice (KO) lacking IgG3. These mice were backcrossed to wild type BALB/c mice (WT) to generate inbred KO BALB/c mice. Genotype and phenotype of mice was confirmed by PCR, Western Blot, ELISA and ELISPOT. KO and WT mice were immunized with 0.5microg of type 3 Pn capsule, Ab titer was measured by ELISA, and then the mice were given 5000, 10,000 or 100,000 cfu of type 3 Pn ip. RESULTS: KO mice had no serum or membrane IgG3 and made anti-PS IgM and IgG1, while WT mice made anti-PS IgM, IgG3 and IgG1 after immunization. WT mice had significantly better survival after Pn challenge. [table: see text] Passive immunization of KO mice with WT sera increased percent survival. CONCLUSION: Mice lacking the dominant IgG subclass made to bacterial PS are more susceptible to fatal pneumococcal sepsis than wild type mice. This model may provide insights into the importance of IgG subclass to anti-pneumococcal immunity.
Publication Types:
Keywords:
- Animals
- Antibodies
- Enzyme-Linked Immunosorbent Assay
- Genes, Immunoglobulin
- Humans
- IgG Deficiency
- Immune Sera
- Immunization, Passive
- Immunoglobulin G
- Mice
- Mice, Inbred C57BL
- Muridae
- Pneumococcal Vaccines
- Polysaccharides, Bacterial
- Sepsis
- Streptococcus pneumoniae
- genetics
- immunology
Other ID:
UI: 102270456
From Meeting Abstracts