Index: Karolinska Institutet: KI North: Department of Medicine, Solna


In vitro generation and evaluation of atypical B cells


Supervisor: Christopher Sundling, PhD, Assistant Professor
Department: Department of Medicine Solna
Postal Address: Bioclinicum J7:20
Infektion/Färnert/Sundling
Visionsgatan 4
171 64 Solna

E-mail: christopher.sundling@ki.se


The B cell response is strongly affected during P. falciparum malaria. This results in the generation of an atypical B cell compartment that has been associated with poor formation of long-lived B cell-mediated immunity. The role the atypical B cells play in immunity remains unknown. Recently, these cells have also been identified in many more infectious diseases, such as HIV, Tuberculosis, Influenza etc, indicating a general mechanism for their generation and suggest that they could haven an important function. Mouse studies have shown similar cells to be excellent antigen-presenting cells, initiating T cell responses, but also to have a regulatory B cell phenotype, that is important for controlling the strength of the immune response.

The aim of this study is to investigate:
1. the capacity of in vitro derived atypical B cells to present antigen to T cells,
2. production of the regulatory cytokine IL-10 in response to stimulation with TLR-ligands.

The main methods include to derive atypical B cell in vitro using interferon-g and BCR stimulation from purified B cells obtained from human buffy coats. The cells will then be fed whole CMV antigen or purified peptides, which are then presented to T cells added to the culture. The regulatory effect of atypical B cells will be investigated by stimulating the cells with the toll-like receptor 9-ligand, CpG, after which interleukin 10 will be measured in the culture supernatant.

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