Memory B-cell function and antibody profiles in malaria : their role in protection against disease in infancy

Malaria infection is of huge public health importance in developing countries, including Uganda. Antibody immunity assumes a paramount part in the disease control however there’s a great need to study components of antibody sustenance and how natural immunity is elicited. Here in this thesis we studied development of P. falciparum specific B-cells and antibodies.

First and foremost we developed a novel flow cytometry method using nano particles (quantum dots) and parasitized red blood cell ghosts that can directly detect P. falciparum specific B-cells in humans. This technique is advantageous for it does not require growth and activation of cells. For the first time using flow cytometry we were able to quantify how much of the B-cell response was directed against malaria. We detected a statistically significant difference in P. falciparum specific B-cells between immune samples (22.3%) and non-immune samples (1.7%). The highest percentage of malaria parasite specific B-cells (27.9%) were observed in individuals with an ongoing malaria infection.

Using the novel flow cytometry technique we studied the development of P. falciparum specific B-cell sub-populations during infancy and in adults. The babies showed increases in P. falciparum specific IgG memory B-cells (MBCs), atypical MBCs, and plasma cells/blasts over time, but the proportion of these cells were still lower than in the mothers who displayed stable levels (5, 18, and 3 %, respectively). P. falciparum specific non-IgG+ MBCs and naïve B-cells binding to P. falciparum antigens were higher in the babies compared to the mothers (12 and 50%). In ELISA there was an increase in IgG and IgM antibodies over time in babies, and stable levels in mothers.

Finally, in another collaborative study, we investigated the antibody anamnestic or memory reaction evoked by a solitary episode of P. falciparum infection. We found that in a larger part (70%) of people, an infection of P. falciparum evokes not less than 20% expansion in level of anti-parasite IgG. This boost in anti-P. falciparum IgG is neither influenced by parasite density on the day of malaria diagnosis, nor HIV status.

In conclusion this thesis advances current knowledge on the development of anti P. falciparum antibodies and P. falciparum specific B-cell sub-populations during infancy and in adults. This information is vital for understanding malaria immunity and future malaria vaccine studies.

List of scientific papers

I. Lugaajju A, Reddy SB, Rönnberg C, Wahlgren M, Kironde F, Persson KEM. Novel flow cytometry technique for detection of Plasmodium falciparum specific B-cells in humans: Increased levels of specific B-cells in ongoing malaria. Malar J. 2015;14:370.
https://doi.org/10.1186/s12936-015-0911-0

II. Lugaajju A, Reddy SB, Wahlgren M, Kironde F, Persson KEM. Development of Plasmodium falciparum specific naïve, atypical, memory and plasma B-cells during infancy and in adults in an endemic area. Malar J. 2017;16:37.
https://doi.org/10.1186/s12936-017-1697-z

III. Kaddumukasa M, Lwanira C, Lugaajju A, Katabira E, Persson KEM, Wahlgren M, Kironde F. Parasite specific Antibody increase induced by an Episode of Acute P. falciparum uncomplicated Malaria. PLoS One. 2015;10(4).
https://doi.org/10.1371/journal.pone.0124297