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Innate Regulation of B Cell Response to Pathogens

Gaya, MN; (2015) Innate Regulation of B Cell Response to Pathogens. Doctoral thesis , UCL (University College London). Green open access

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Abstract

B cells are a group of lymphocytes that contribute to the adaptive immune response by producing highly specific antibodies against pathogenic antigens. In vivo, B cells get activated when they recognise a specific antigen on the surface of presenting cells through their B cell receptor. Among these cells, a population of macrophages at the lymph node subcapsular sinus has recently emerged as a key player in the presentation of antigen to B cells. Following antigenic stimulation, B cells process and present pathogen-derived peptides to specific CD4+ T cells, what induces B cell proliferation and differentiation into antibody secreting cells. Moreover, it was recently found that an innate-like population of T cells named natural killer T cells could also provide cognate help to B cells in response to lipid antigens. The aim of this thesis is to investigate the functional role of subcapsular sinus macrophages and natural killer T cells in the B cell response to infectious pathogens. To this end, I combined a number of innovative imaging approaches with the generation of a new series of transgenic mouse strains and infectious models. I found, in short, that virus and bacteria-induced inflammation triggers a temporary disruption of the subcapsular sinus macrophage organisation, resulting in diminished antigen capture and B cell responses to secondary infections. Furthermore, I unveiled a new way in which iNKT cells get activated and regulate germinal centre responses during respiratory viral infections. These findings are important as they shed light on some of the regulatory mechanisms for antigen encounter and B cell response during infection.

Type: Thesis (Doctoral)
Title: Innate Regulation of B Cell Response to Pathogens
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1473388
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