Germinal centre and marginal zone B cells expand quickly in a second Plasmodium chabaudi malaria infection producing mature plasma cells

R Stephens,J Langhorne,F M Ndungu

doi:10.1111/j.1365-3024.2008.01066.x

Abstract

Antibodies and B cells are critical in the protective immune response to the blood stage of the malaria parasite, Plasmodium chabaudi. However, little is known about the development of memory B cells and their differentiation into plasma cells during infection or after re-infection. Here we have shown that B cells with phenotypic characteristics of memory cells (CD19+IgD− CD38+, IgG1+) are generated in a primaryPlasmodium chabaudi chabaudi infection of mice. In addition, we observed that germinal centre cells (CD19+, GL7+, MHCIIhi) and Marginal Zone B cells (CD19+CD23−IgD−) show faster expansion on re-infection than in the primary, though other subsets do not. Interestingly, though both IgM− and IgM+ memory cells are produced, IgM+ memory cells do not expand on second infection. The second infection quickly produced mature bone marrow plasma cells (intracellular Ighi, CD138hi, CD9+, B220−), compared to primary infection; which generates a very large population of immature splenic plasma cells (B220+). This analysis suggests that a memory B cell population is generated after a single infection of malaria, which on re-infection responds quickly producing germinal centres and generating long-lived plasma cells making the second encounter with parasite more efficient.

Highlights

Immunity to malaria is slow to develop, and prevalence and levels of parasitaemia decrease with exposure, susceptibility to re-infection remains for years even after repeated exposure [1,2]
Antibodies are considered to be a major effector mechanism eliminating blood-stage malaria parasites in humans [4,5], and in experimental models [6,7], and it is possible that impairment of protective immunity is due to defects in the B cell response
Plasmodium chabaudi infection in mice does stimulate significant malaria-specific antibody responses, and we have shown that kinetics of MSP-1 specific antibody production on re-challenge are enhanced, a result compatible with the normal generation of memory B cells [15]

Summary

Introduction

Immunity to malaria is slow to develop, and prevalence and levels of parasitaemia decrease with exposure, susceptibility to re-infection remains for years even after repeated exposure [1,2]. [8]), there are very few cellular studies investigating the nature and development of the antibody-producing cells; B cells and plasma cells Those studies, describing large short-lived polyclonal B cell responses [9,10,11], changes in splenic microarchitecture [12] and B cell compartments such as germinal centres [13], and deletion of malariaspecific B cells after acute infection [14], suggest that the B cell response and resulting memory to Plasmodium may be impaired. Studies of the nature of the plasma cell response will be important to discern reasons for the short-lived components of the antibody response to human malaria [8]

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Results

Discussion

Conclusion