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Infection and Immunity, November 2005, p. 7477-7484, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7477-7484.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Light Chain Repertoire

S. Louise Smithson, Kris Kolibab, Anne K. Shriner, Neeti Srivastava, Sadik Khuder, and M. A. Julie Westerink*

Department of Medicine, Medical University of Ohio, Toledo, Ohio

Received 17 June 2005/ Returned for modification 26 July 2005/ Accepted 24 August 2005

Streptococcus pneumoniae is a human bacterial pathogen responsible for serious infections including pneumonia. The currently licensed polysaccharide vaccine provides 60 to 80% protection in young adults, but in the elderly the vaccine efficacy is drastically reduced despite normal antibody levels. We hypothesized that the reduced vaccine efficacy in the elderly results from altered variable gene family usage. We have analyzed the light chain gene usage in 20 young (20 to 30 years of age) and 20 elderly (65 to 86 years of age) adults in response to pneumococcal polysaccharide 4 (PPS4) and PPS14. We generated a variable light chain library using B cells specific for PPS4 and PPS14 from each vaccinated individual. We determined complete sequences and somatic mutation frequencies in all isolated variable light chain fragments. Six gene families, {kappa}1, {kappa}2, {kappa}3, {kappa}4, {lambda}1, and {lambda}3, were identified in response to PPS4 and PPS14 in both age groups. Comparison of young and elderly adults demonstrated significant differences in {kappa}4, {lambda}1, and {lambda}3 gene usage in response to PPS4 and PPS14. With aging, there was a significant increase in {kappa}4 gene usage and a significant decrease in {lambda}1 and {lambda}3 gene usage in response to both PPS4 and PPS14. Although both V{kappa}1 and V{lambda}3 gene products demonstrated extensive mutations, there was no age-related difference in mutational frequency per gene family. These findings suggest an age-related change in light chain gene usage in response to PPS4 and PPS14.

* Corresponding author. Mailing address: Department of Medicine, Medical University of Ohio, Health Education Building, 3000 Arlington Avenue, Toledo, OH 43614. Phone: (419) 383-6097. Fax: (419) 383-3075. E-mail: mwesterink{at}meduohio.edu.

Editor: T. R. Kozel

Infection and Immunity, November 2005, p. 7477-7484, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7477-7484.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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