Exploring B cell responses in Plasmodium falciparum malaria
Author: Rönnberg, Caroline
Date: 2019-11-08
Location: Gardaulan, Folkhälsomyndigheten, Nobels väg 18, Solna
Time: 10.00
Department: Inst för mikrobiologi, tumör- och cellbiologi / Dept of Microbiology, Tumor and Cell Biology
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Thesis (2.636Mb)
Abstract
Plasmodium falciparum malaria remains one of the most devastating infectious
diseases today. Small children in sub-Saharan Africa carry the heaviest burden
of morbidity and mortality. Immunity to malaria is not well understood, although
humoral immunity has proven an integral part of protection from disease.
Antibodies
are produced by B cells and have been directly linked to clinical immunity to
malaria. There is a need to further characterize the development of B cell responses
during and following a malaria infection, in order to understand the basis of
clinical immunity. In Study I we developed a method for the identification of P.
falciparum-specific B cells using Quantum dots in flow cytometry. We found
almost a third of B cells from individuals living in a malaria-endemic area to be
specific for P. falciparum. In Study II we followed a cohort of mothers and infants
in Uganda with prospective blood sampling from birth up to nine months. Levels
of the cytokine, B cell activating factor, were measured and in infants found to
be highest in cord blood with a subsequent decrease, while the levels in mothers
remained stable. Furthermore, B cell activating factor was inversely correlated
with IgG+ memory B cells and CD27- memory B cells at different time points in
infants and mothers. Study III was a prospective study in Stockholm enrolling
individuals with acute malaria with subsequent sampling over a year. We found
that B cells responding to infection with P. falciparum expressed CD11c with a
dynamic shift within B cell compartments. Differences between individuals with
a primary malaria infection and those previously infected, revealed differential
expansion with a higher frequency of atypical memory B cells in previously
infected individuals. In Study IV we established a novel co-culture method for
human B cells and P. falciparum-infected red blood cells to mimic in vivo conditions.
Parasitemia increased more rapidly when parasites were cultured with B
cells than when cultured alone, and B cells exhibited phenotypic changes after ten
days in co-culture with P. falciparum. Within the scope of this thesis we provide
new methodology for the study of B cell responses to malaria, and present longitudinal
data on B cell remodeling after acute malaria, as well as B cell activating
factor in an endemic area. These novel methods and findings contribute valuable
knowledge and can be used to inform the design of future studies to increase our
understanding of the immune system in malaria.
List of papers:
I. Allan Lugaajju, Sreenivasulu B. Reddy, Caroline Rönnberg, Mats Wahlgren, Fred Kironde and Kristina E. M. Persson. Novel flow cytometry technique for detection of Plasmodium falciparum specific B-cells in humans: increased levels of specific B-cells in ongoing infection. Malar J 2015, 14:370.
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II. Caroline Rönnberg, Allan Lugaajju, Anna Nyman, Ulf Hammar, Matteo Bottai, Christopher Sundling, Fred Kironde, Kristina E M Persson. A longitudinal study of plasma BAFF levels in mothers and infants in Uganda. [Manuscript]
III. Christopher Sundling*, Caroline Rönnberg*, Victor Yman, Muhammad Asghar, Peter Jahnmatz, Tadepally Lakshmikanth, Yang Chen, Jaromir Mikes, Mattias N. Forsell, Klara Sondén, Adnane Achour, Petter Brodin, Kristina E.M. Persson, and Anna Färnert. B cell profiling in malaria reveals expansion and remodeling of CD11c+ B cell subsets. JCI Insight. 2019; 4(9):e126492. * Equal contribution.
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IV. Sreenivasulu B. Reddy, Noemi Nagy, Caroline Rönnberg, Francesca Chiodi, Allan Lugaajju, Frank Heuts, Laszlo Szekely, Mats Wahlgren, Kristina E. M. Persson. Direct contact between Plasmodium falciparum and human B-cells affects parasite growth and FcRL4 expression in novel long-term co-culture method. [Submitted]
I. Allan Lugaajju, Sreenivasulu B. Reddy, Caroline Rönnberg, Mats Wahlgren, Fred Kironde and Kristina E. M. Persson. Novel flow cytometry technique for detection of Plasmodium falciparum specific B-cells in humans: increased levels of specific B-cells in ongoing infection. Malar J 2015, 14:370.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Caroline Rönnberg, Allan Lugaajju, Anna Nyman, Ulf Hammar, Matteo Bottai, Christopher Sundling, Fred Kironde, Kristina E M Persson. A longitudinal study of plasma BAFF levels in mothers and infants in Uganda. [Manuscript]
III. Christopher Sundling*, Caroline Rönnberg*, Victor Yman, Muhammad Asghar, Peter Jahnmatz, Tadepally Lakshmikanth, Yang Chen, Jaromir Mikes, Mattias N. Forsell, Klara Sondén, Adnane Achour, Petter Brodin, Kristina E.M. Persson, and Anna Färnert. B cell profiling in malaria reveals expansion and remodeling of CD11c+ B cell subsets. JCI Insight. 2019; 4(9):e126492. * Equal contribution.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Sreenivasulu B. Reddy, Noemi Nagy, Caroline Rönnberg, Francesca Chiodi, Allan Lugaajju, Frank Heuts, Laszlo Szekely, Mats Wahlgren, Kristina E. M. Persson. Direct contact between Plasmodium falciparum and human B-cells affects parasite growth and FcRL4 expression in novel long-term co-culture method. [Submitted]
Institution: Karolinska Institutet
Supervisor: Persson, Kristina
Co-supervisor: Färnert, Anna; Chiodi, Francesca; Sundling, Christopher
Issue date: 2019-10-18
Rights:
Publication year: 2019
ISBN: 978-91-7831-584-2
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