Natkanski, EM;
(2013)
Investigating Novel Components and Mechanisms Involved in B Cell Receptor-Antigen Internalisation.
Doctoral thesis , UCL (University College London).
![]() |
PDF
Elizabeth Natkanski PhD Thesis.pdf Available under License : See the attached licence file. Download (40MB) |
![]() |
AVI video (Supplement: Movie 1: B1 8 B cells on antigen)
Movie_1_B1_8_B_cells_on_antigen_loaded_PLB.avi Download (2MB) |
![]() |
AVI video (Supplement: Movie 2: B16 B cells on antigen)
Movie_2_Bl6_B_cells_on_antigen_loaded_PMS.avi Download (12MB) |
![]() |
AVI video (Supplement: Movie 3: Dil stained invaginations and antigen microclusters)
Movie_3_DiI_stained_invaginations_and_antigen_microclusters.avi Download (4MB) |
![]() |
AVI video (Supplement: Movie 4: B16 B cell expressing Clathrin light chain GFP on antigen loaded PMS)
Movie_4_Bl6_B_cell_expressing_Clathrin_light_chain_GFP_on_antigen_loaded_PMS.avi Download (13MB) |
![]() |
AVI video (Supplement: Movie 5: BL6 B cells expressing Myosin IIA RLC GFP on DiD stained antigen loaded PMS)
Movie_5_BL6_B_cells_expressing_Myosin_IIA_RLC_GFP_on_DiD_stained_antigen_loaded_PMS.avi Download (3MB) |
![]() |
AVI video (Supplement: Movie 6: B16 B cells expressing LifeAct on DiD stained Antigen loaded PMS)
Movie_6_Bl6_B_cells_expressing_LifeAct_on_DiD_stained_Antigen_loaded_PMS.avi Download (5MB) |
Abstract
The elimination of a wide variety of infections requires the production of high affinity antibodies specific for the invading pathogen. The generation of these high affinity antibodies depends on the ability of B cells to recognise and internalise antigens from the surface of antigen-presenting cells (APCs) in an affinity-dependent manner. B cells expressing high affinity B cell receptors (BCRs) internalise, process and present more antigen, obtain better T cell help, and are selectively expanded over lower affinity equivalents. However, the molecular mechanisms by which B cells extract antigens for presentation remain unclear. Using a new fluid and flexible membrane substrate to mimic APCs, we show that B cells acquire antigen by dynamic myosin IIA-mediated contractions that pull out and invaginate the presenting membranes. Invaginations containing high affinity BCR-antigen microclusters were able to withstand the force of these contractions and recruit clathrin resulting in endocytosis. In contrast, low affinity BCR-antigen bonds quickly ruptured aborting internalisation. Thus we conclude that coupling contractility to endocytosis permits B cells to discriminate between antigen affinities, which provides a mechanism for the selective advantage seen for high affinity B cell clones in vivo. Disruptions in BCR-antigen internalisation has been linked to the growth of malignant B cells and the development of autoimmunity. Therefore, ultimately, our results could contribute to the effective design of future therapeutics for B cell diseases.
Type: | Thesis (Doctoral) |
---|---|
Title: | Investigating Novel Components and Mechanisms Involved in B Cell Receptor-Antigen Internalisation |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Keywords: | B cell receptor |
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 Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
URI: | https://discovery.ucl.ac.uk/id/eprint/1413024 |
Archive Staff Only
![]() |
View Item |