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Infection and Immunity, February 2006, p. 1025-1031, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1025-1031.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Correlation of Molecular Characteristics, Isotype, and In Vitro Functional Activity of Human Antipneumococcal Monoclonal Antibodies

H. E. Baxendale* and D. Goldblatt

Infectious Diseases, Microbiology, and Immunobiology Units, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom

Received 28 September 2005/ Returned for modification 14 October 2005/ Accepted 27 October 2005

Structure-function correlations of pneumococcal antibodies are important in predicting how changes in the pneumococcus (Pnc)-specific B-cell repertoire will influence humoral immunity against invasive Pnc disease. Using a unique panel of human hybridomas derived from memory B cells after pneumococcal conjugate vaccination, we analyzed the structure-function relationship of nine monoclonal antibodies (MAbs) reactive to Pnc polysaccharides. The avidities of the antibodies correlated with the avidity of donor immune serum (R, 0.7; P < 0.025), and this relationship was particularly strong for immunoglobulin A clones (R, 1; P < 0.0005), suggesting that the MAbs may represent important clones contributing to serological memory. Common heavy-light chain combinations and amino acid replacement mutations were seen for clones with the same serospecificity from different individuals. The two highest-avidity MAbs used Vh3-48, and two MAbs with the same serospecificity, using the same V gene pairings (Vh3-7 and Vk2A17), had similar avidities, suggesting that canonical V gene use makes an important contribution to avidity. Although all clones had mutation levels consistent with their being derived from memory B cells, low levels of replacement mutation were associated with high avidities. This relationship was strongest for Vh genes (R, 0.8; P < 0.01). Opsonophagocytosis was demonstrated for all clones, and there was a trend toward clones using canonical genes with low levels of mutation having high opsonophagocytic activities (R, 0.5). These data suggest that the use of canonical genes in the Pnc antibody response is associated with highly functional antibodies and that most somatic mutations seen in these genes are not antigen selected.

* Corresponding author. Mailing address: Infectious Diseases and Microbiology Unit, Institute of Child Health, University of London Medical School, 30 Guilford St., London WC1N 1EH, United Kingdom. Phone: 44 207 905 2370. Fax: 44 207 813 8494. E-mail: H.Baxendale{at}ich.ucl.ac.uk.

Editor: J. N. Weiser

Infection and Immunity, February 2006, p. 1025-1031, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1025-1031.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tian, H., Weber, S., Thorkildson, P., Kozel, T. R., Pirofski, L.-a. (2009). Efficacy of Opsonic and Nonopsonic Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibodies against Intranasal Challenge with Streptococcus pneumoniae in Mice. Infect. Immun. 77: 1502-1513 [Abstract] [Full Text]  


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