The B lymphoid lineage: activation and subsets

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The B lymphoid lineage activation and subsets

• Simon Hunt
• Dunn School of Pathology
• email simon.hunt_at_path.ox.ac.uk
• You are welcome to use the material in this
  lecture for your own private study further
  distribution is not allowed. Available by link
  from http//www.psb.ox.ac.uk/Newfhs/09imm.htm

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The BIG questions 27 May 2003
Why Humoral as well as Cell-Mediated? How
regulate the choice? Contribution to overall
immunity incl Innate? B cell tolerance How?
Why some AutoAb specificities, not others? IgD
function? Ig expression control, class-switching,
esp to IgE? B memory how? Is there a distinct
memory cell? Affinity Maturn? B cell subsets
- why?? Why doesnt immune system get bigger and
bigger with repeated stimulation?
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The B cell lineageLing, NR (1988) in B
lymphocytes in Human Disease p.175
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LN architecture

• T and B cells are segregated
• Instant snapshot view but in fact is very
  dynamic so cells can contact
• Chronic inflammation ? organised lymphoid
  structure
• Cytokine-dependent
• B lymphocyte chemokine, BLC (Cyster, 1999)
• Lymphotoxin, TNF (Chaplin, 1999)

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Ectopic B and T areas

• Transgenic expression of BLC under insulin
  promoter
• Pancreatic expression
• Pancreatic pseudo-LN!
• NB use of CarboxyFluorescein succinimidyl ester
  for cell tracking

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Effects of Lymphotoxin, LTß, and TNF on lymphoid
tissue architecture
After Fu and Chaplin Ann Rev Immunol 17 399
(1999)
-/-
 
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Germinal centre reaction
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B cell signalling in GC reaction
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B-T inter-actions
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Two signals for B cells
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B cell sIg cross-linking
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T cells and cytokines in antibody production
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Normal B cell ontogeny
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Lymphoma cell of origin
From http//www.path.sunysb.edu/hemepath/tutorial/
default.htm
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Lymphochip micro-array of cDNAs from lymphoid
cells
1. Hybridise cDNA from tissue of interest (tagged
one colour) compared with cDNA from reference
tissue (another colour) 2. Measure ratio of the
two fluorescent colours for each spot of cloned
cDNA 3. Computer sorts out high and low binders

17856 cDNA clones
http//www.cdc.gov/ncidod/eid/vol6no5/cummings2G.h
tm
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cDNA gene expression profiling on Lympho-chip
micro-array
13637 Genes heirarchically grouped by computer
after analysis
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cDNA expression profiling on Lympho-chip detail
T lymphocytes B lymphocytes Follicular lymphoma
T
B
F
Purple gt mean Yellow lt mean
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Classification of lymphomas

• http//llmpp.nih.gov/lymphoma/

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Summary

• Thelpers in collaboration with B cells
• Hapten-carrier is explained as B-T interaction
• Response induction extrafollicularly
• In T cell area
• Germinal centre reaction
• Hypermutation and interaction with activated CD4
  T cells and FDC
• Anti-apoptotic signals
• Lymphocyte subsets
• Naïve
• Memory
• Marginal Zone B cells
• B1 B cells
• Still some BIG questions left.