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Infant B cell responses to polysaccharide determinants
G T Rijkers1, E A Sanders, M A Breukels
1Department of Immunology, University Hospital for Children and Youth, Wilhelmina's Children Hospital, Utrecht, The Netherlands. grijkers@wkz.azu.nl
Insights
Infants under two years cannot produce antibodies to bacterial polysaccharides, increasing infection risk. Conjugate vaccines overcome this, inducing a protective IgG1 antibody response in young children.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
Background:
- Infants under 2 years are susceptible to encapsulated bacterial infections due to an inability to produce antibodies against bacterial capsular polysaccharides.
- Bacterial capsular polysaccharides are T cell independent type 2 antigens that typically induce IgG2 antibodies.
- Neonatal B lymphocytes show reduced expression of CD21 (type 2 complement receptor), a key co-stimulatory molecule for polysaccharide recognition, explaining unresponsiveness.
Purpose of the Study:
- To investigate the immunological basis for infant unresponsiveness to polysaccharide antigens.
- To evaluate the efficacy of polysaccharide-protein conjugate vaccines in overcoming early-life unresponsiveness.
Main Methods:
- Analysis of B lymphocyte activation mechanisms in neonates and infants.
- Assessment of antibody production in response to polysaccharide antigens and conjugate vaccines.
Main Results:
- Neonatal B lymphocytes exhibit reduced CD21 expression, impairing responses to polysaccharides.
- Polysaccharide-protein conjugate vaccines effectively induce an immune response in infants.
- The induced antibody response to conjugate vaccines is predominantly IgG1, differing from the typical IgG2 response to unconjugated polysaccharides.
Conclusions:
- Reduced CD21 expression on neonatal B cells contributes to poor responses to bacterial polysaccharides.
- Polysaccharide-protein conjugate vaccines are a viable strategy to induce protective immunity against encapsulated bacteria in early infancy.
Abstract:
Newborns and infants up to the age of 1.5-2 years of age are unable to produce antibodies to bacterial capsular polysaccharides. As a consequence, children up to the age of 2 years have an increased susceptibility for infections with encapsulated bacteria. Capsular polysaccharides are classified as so-called T cell independent type 2 antigens and induce IgG2 antibodies. The mechanism of B lymphocyte activation by polysaccharides differs from that of protein antigens and involves co-stimulation by CD21 (type 2 complement receptor). Reduced expression of CD21 on neonatal B lymphocytes can explain unresponsiveness to polysaccharides. Polysaccharide protein conjugates have the ability to overcome unresponsiveness to polysaccharides early in life. The response induced is predominant IgGl.