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Infection and Immunity, August 2002, p. 4083-4091, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4083-4091.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Recurrent Variable Region Gene Usage and Somatic Mutation in the Human Antibody Response to the Capsular Polysaccharide of Streptococcus pneumoniae Type 23F

Jianhui Zhou,1 Kathleen R. Lottenbach,2 Stephen J. Barenkamp,2 Alexander H. Lucas,1 and Donald C. Reason1*

Children's Hospital Oakland Research Institute, Oakland, California 94609,1 Health Sciences Center, St. Louis University School of Medicine, St. Louis, Missouri 631102

Received 20 February 2002/ Returned for modification 28 March 2002/ Accepted 19 April 2002

Combinatorial cloning and expression library analysis were used to isolate human antibody Fab fragments specific for the capsular polysaccharide of Streptococcus pneumoniae serotype 23F. Thirty 23F-specific Fabs were isolated from seven vaccinated donors, and the sequences of the heavy (H)- and light (L)-chain variable regions were determined. All individuals utilized either the V{kappa} A23 L chain, the V{kappa} L6 L chain, or both chains in forming the 23F-specific combining site. V{kappa} A23 L chains paired primarily with VH3-23 H chains. V{kappa} L6 L chains were more promiscuous in heavy-chain usage between individuals. Both H and L chains were mutated, primarily in the complementarity-determining regions, compared to their closest germ line counterpart, suggesting a recall response that has undergone affinity maturation. H-chain isotypes were reflective of those found in the serum. Shared somatic modifications demonstrated that immunoglobulin G2 (IgG2) and IgA antibodies arose from the same somatically matured B cell. Our results indicate that the response to the serotype 23F pneumococcal capsular polysaccharide is oligoclonal within the individual, with one or two paratope families accounting for the majority of expressed antibody. We also determined that, in spite of the combinatorial diversity available to the immune system, the 23F-specific response is highly restricted at the population level, with the same two L-chain-determined paratope families recurring in all individuals. Lastly, analysis of the isolated Fabs indicate all have undergone extensive somatic mutation, as well as class switch, maturational events that presumably require the participation of T cells.

* Corresponding author. Mailing address: Children's Hospital Oakland, Research Institute, 5700 Martin Luther King, Jr., Way, Oakland, CA 94609. Phone: (510) 450-7638. Fax: (510) 601-3911. E-mail: dreason{at}chori.org.

Editor: D. L. Burns

Infection and Immunity, August 2002, p. 4083-4091, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4083-4091.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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