10. B Cell Differentiation

Question 1

What are B cells?

Answer 1

Cells that express unique receptors that only recognise one target - BCR surface or surface Ig
Involved in diseases such as autoimmunity and cancer
Also in vaccination - inducing antibodies key aim of vaccination
B cells can develop into plasma cells or memory B cells and provide protection by producing antibodies

Question 2

How many populations of B cells?

Answer 2

Follicular - BZ
Marginal zone - MZ
BI

Question 3

Why is it important to study B cell differentiation?

Answer 3

Produce antibodies that bind antigens - neutralisation, opsonisation, complement activation
Different version nature of B cells responses
Also play regulatory role in infection autoimmunity and cancer that may be antigen specific or non-specific - B reg
Number of immune deficiencies caused by gene defects of disease or infection
Children without antibodies experience a lot more disease

Question 4

B reg cells

Answer 4

Inhibition of autoimmune response

Inhibition of anti-tumour responses - many cancers derive from B cells: myeloma, leukaemia, lymphoma e.g. burkitt’s

Question 5

What are the 3 pathways that make plasma cells and Ab?

Answer 5

1. B1 cells make natural Ig e.g. IgM and/or IgA without stimulus to limited repertoire of antigens. T-independent
2. Extrafollicular responses. T independent and T dependent depending on antigen Ab affinity low
3. Germinal centres high affinity memory B cells T- dependent

Question 6

Preventing autoimmunity

Answer 6

Soluble self and low affinity, no crosslinking self
-> migrate to periphery anergic B cell, mature (clonally ignorant)
Prevent survival of B cells that recognises self
Multivalent self molecule - clonal deletion rediting

Question 7

Negative and positive stages of tolerance for B cells

Answer 7

Negative - BM: open repertoire of mature B cells, tolerance induction; blood and 20 lymphoid tissues
- additional tolerance induction self tolerant and allergies

Positive - No: fail to enter lymphoid follicle 1/2 life ~3 days; enter lymphoid follicles - stimulation by antigen

Question 8

The molecular profile of developing B cell change depending upon what?

Answer 8

Their stage of development

High degree of complexity in development

Question 9

Where do B cells develop on?

Answer 9

Stromal cells
As B cells develop they migrate within BM
Cells differ at different stages
Responses to antigens = antibody bind antigen -> internalised by receptor mediated endophytes is - high density of specific antigen fragments presented
Generation of primary T dependent response

Question 10

Generation of primary T dependent responses

Answer 10

Virgin or memory B cells on binding antigen move to T zone increases CCR7
Naive T cells are primed by cognate interaction with DC
(T zone) cognate interaction of primed T and and Ag activated B cells
(Medulla) Extrafollicular plasmablast resulting in rapid Ab production
(Follicle) germinal centres gradually produce persistent high affinity Ab and memory B cells

Question 11

B cells develop in a series of sequential steps

Answer 11

Early pro B cell - DJ rearrangement first
Late pro B cell - followed you rearrangement with the U gene
Large pre B cell - division, there is a functional an chain, pre BCR needs surrogate chain for surface expression
Small pre B cell - intracellular m chain, V-J rearranging
Immature B cells - IgM expressed at cell surface, if cell strongly binds antigen elimated negative selection
Mature B cell - IgD/IgM made from alternately spliced H chain transcripts