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Infection and Immunity, January 2006, p. 257-264, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.257-264.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Target Antigen, Age, and Duration of Antigen Exposure Independently Regulate Immunoglobulin G Subclass Switching in Malaria

J. Eric Tongren,1 Christopher J. Drakeley,1,2 Suzanna L. R. McDonald,1 Hugh G. Reyburn,1,2 Alphaxard Manjurano,2 Watoky M. M. Nkya,1,3 Martha M. Lemnge,1,4 Channe D. Gowda,5 Jim E. Todd,1 Patrick H. Corran,1,6 and Eleanor M. Riley1*

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom,1 Joint Malaria Programme, P.O. Box 2228, Moshi, Tanzania,2 Kilimanjaro Christian Medical Centre, P.O. Box 3010, Moshi, Tanzania,3 Amani Medical Research Institute, National Institute for Medical Research, P.O. Box 4, Amani, Tanzania,4 Pennsylvania State University School of Medicine, Hershey, Pennsylvania,5 National Institute for Biological Standards & Control, South Mimms, Herts EN6 3QG, United Kingdom6

Received 30 August 2005/ Returned for modification 18 September 2005/ Accepted 24 September 2005

The isotype/subclass of immunoglobulin determines antibody function, but rather little is known about factors that direct class switching in vivo. To evaluate factors that might influence the maturation of the antibody response during infection, we conducted a seroepidemiological study of the immunoglobulin G (IgG) subclass response to four merozoite-associated antigens of Plasmodium falciparum in a mountainous region of northeastern Tanzania, where malaria endemicity declines with increasing altitudes. We found that IgG1/IgG3 class switching is independently affected by the nature of the antigen, cumulative exposure to the antigen, and the maturity of the immune system (i.e., the age of the individual). These observations provide insights into the effects of immune system maturity, the duration and intensity of antigen exposure, and inherent characteristics of individual antigens on the process of class switching in human B cells. Our data also throw light on the consequences of class switch decisions on the gradual acquisition of antimalarial immunity.

* Corresponding author. Mailing address: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, United Kingdom. Phone: (44) 207 927 2706. Fax: (44) 207 927 2807. E-mail: eleanor.riley{at}lshtm.ac.uk.

Editor: W. A. Petri, Jr.

Infection and Immunity, January 2006, p. 257-264, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.257-264.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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