| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852;
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; and
¶ Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852
Despite the central role of memory B cells (MBC) in protective immune responses, little is understood about how they are acquired in naive individuals in response to Ag exposure, and how this process is influenced by concurrent activation of the innate immune system’s TLR. In this longitudinal study of malaria-naive individuals, we examined the MBC response to two candidate malaria vaccines administered with or without CpG, a TLR9 ligand. We show that the acquisition of MBC is a dynamic process in which the vaccine-specific MBC pool rapidly expands and then contracts, and that CpG enhances the kinetics, magnitude, and longevity of this response. We observed that the percentage of vaccine-specific MBC present at the time of reimmunization predicts vaccine-specific Ab levels 14 days later; and that at steady-state, there is a positive correlation between vaccine-specific MBC and Ab levels. An examination of the total circulating MBC and plasma cell pools also suggests that MBC differentiate into plasma cells through polyclonal activation, independent of Ag specificity. These results provide important insights into the human MBC response, which can inform the development of vaccines against malaria and other pathogens that disrupt immunological memory.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; by contract N01-AI-25460 from the National Institutes of Health (to D.J.T. and J.J.T.); and by UL1 RR024160 from the National Center for Research Resources (to U.R.M.C.).
2 Address correspondence and reprint requests to Dr. Peter D. Crompton, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook 2 Building, Room 200F, 12441 Parklawn Drive, Rockville, MD 20852. E-mail address: pcrompton{at}niaid.nih.gov
3 Current address: MedImmune, Gaithersburg, MD 20878.
4 Abbreviations used in this paper: MBC, memory B cells; AMA1-C1, apical membrane Ag 1-combination 1; ASC, Ab-secreting cells; GEE, generalized estimating equations; KLH, keyhole limpet hemocyanin; LLPC, long-lived plasma cell; MSP142-C1, merozoite surface protein 142-combination 1; PC, plasma cell; PDC, plasmacytoid dendritic cell; SAC, protein A from Staphylococcus aureus Cowan; VZV, varicella-zoster virus 1.
This article has been cited by other articles:
|
|
 |
|
  M. Bonsignori, M. A. Moody, R. J. Parks, T. M. Holl, G. Kelsoe, C. B. Hicks, N. Vandergrift, G. D. Tomaras, and B. F. Haynes HIV-1 Envelope Induces Memory B Cell Responses That Correlate with Plasma Antibody Levels after Envelope gp120 Protein Vaccination or HIV-1 Infection J. Immunol., August 15, 2009; 183(4): 2708 - 2717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Weiss, P. D. Crompton, S. Li, L. A. Walsh, S. Moir, B. Traore, K. Kayentao, A. Ongoiba, O. K. Doumbo, and S. K. Pierce Atypical Memory B Cells Are Greatly Expanded in Individuals Living in a Malaria-Endemic Area J. Immunol., August 1, 2009; 183(3): 2176 - 2182. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
