Gray, David

Morrison, Vicky L.

Medical Research Council (MRC)

Wellcome Trust

2011-05-24T11:14:47Z

2011-05-24T11:14:47Z

2011

B cells recognise antigens on micro-organisms through their B cell receptor (BCR) and via Toll-like receptors (TLRs), and thus respond in both innate and adaptive manners during the subsequent immune response. Innate recognition through TLRs has the potential to alter the behaviour of whole B cell populations. I show, here, that MyD88-dependent activation of B cells via TLR2 or TLR9 causes the rapid loss of expression of CD62L, by metalloproteinasedependent shedding, resulting in the exclusion of these cells from lymph nodes and Peyer’s patches, but not the spleen. Moreover, systemic infection with Salmonella typhimurium causes shedding of CD62L and the subsequent focussing of B cell migration to the spleen. I reveal that splenic B cells undergo further changes during S. typhimurium infection, including TLR-dependent differentiation of marginal zone B cells into IgM-secreting plasma cells. Together, these TLR-mediated alterations to B cells are likely to influence the development of immunity to pathogens carrying the appropriate ligands. In addition to these innate responses of B cells, endocytosis of cognate antigen through their BCR allows antigen presentation. This, together with their ability to secrete cytokines, means they have the potential to drive T helper cell responses. I investigate the role of B cells in such CD4+ T cell responses by following antigen-specific T cells in vivo, using both a peptide immunisation strategy and the S. typhimurium infection model. I use anti-CD20 B cell depletion antibodies to deplete B cells at various stages of the immune response, and analyse the effects on T follicular helper and memory cell populations. I show that both the generation and maintenance of T follicular helper cells is dependent on the presence of B cells. Furthermore, I demonstrate that B cells are necessary very early in immune responses, during the first 10 days, for efficient generation of memory T cells.

http://hdl.handle.net/1842/4873

en

The University of Edinburgh

Vicky L. Morrison, Tom A. Barr, Sheila Brown and David Gray, TLR-Mediated Loss of CD62L Focuses B Cell Traffic to the Spleen during Salmonella typhimurium Infection, The Journal of Immunology 185: 2737-2746

B cells

antigen presentation

memory

salmonella

TLR

Toll-like receptors

Innate and cognate roles of B cells in T cell differentiation and memory

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy