Lecture 22: Cellular Interactions and Trafficking - B cells Flashcards
Following development, what can B cells mature into?
B-1 B cells and B-2 B cells which can differentiate into follicular or marginal zone B-2 B cells
What are characteristics of B-1 B cells?
progenitors distinct from B-2 B cells
mostly recognise capsular polysaccharide antigens
able to produce IgM without T cell help
What are the different types of B-2 B cells?
marginal zone, follicular and memory B cells
Why is there continual competition for entry of B-2 B cells?
due to limited number of follicles which favour established B cells
Where are marginal zone B cells found?
in the marginal zones of the white pulp
What is the role of marginal zone B cells?
poised to make rapid responses to blood-borne antigens
relatively broad specificity
What responses do marginal zone B cells produce?
typically T cell independent responses and does not generate memory
What are follicular B cells and what do they express?
form the majority of B cells and are involved in the co-expression of IgM and IgD
What are follicular B cells capable of? What is their activation threshold like?
recirculating through lymphoid tissues
higher activation threshold for proliferation and differentiation
What is the role of memory B cells?
rapid response to re-encounters
Why are memory B cells usually less differentiated?
so they have the ability to refine Ab affinity
What is the role of B cell responses?
antibody secretion to protect from extracellular pathogens and toxins
What are antibodies involved in?
neutralisation, opsonisation and complement activation
What do B cell responses require in order to be activated?
require activation of naive B cells
require multiple signals
When do T cell independent responses occur?
typically with highly repetitive molecules such as polysaccharides of bacterial cell walls
What do T cell independent responses involve?
activation of B cells without T cell help
activated by the cross linking of BCRs
What are T cell independent responses normally limited to?
usually limited to IgM but cytokines may enhance response
What is required for the activation of T cell dependent responses?
require multiple signals to induce efficient responses
dependent on CD40/CD40L interaction between B cells and Tfh
What is important in maintenance of self-tolerance?
both CD4 T cells and B cells have to to be activated during a T cell response
How are antigens detected by B cells?
native antigen can passively drain through lymphatics
key roles for other cell types in active presentation e.g. subcapsular macrophages and follicular dendritic cells
Where are subcapsular macrophages found?
in subcapsular sinus of LNs and marginal sinus of the spleen
What is the role of subscapular macrophages?
able to take up antigen but does not degrade them
decorates the surface with antigen
What are follicular dendritic cells and where are they found?
not dendritic cells but stromal cells which are found embedded throughout the follicles
What type of cell are follicular dendritic cells?
non-phagocytic cell of non-hematopoietic origin
What is the role of follicular dendritic cells?
presents antigen to B cells
What do most humoral responses require?
require B cells to interact with T cells
Why do B cells reside in follicles and what happens following activation?
due to expression of CXCR5 which is attracted to CXCL13
B cells upregulate CCR7 to move towards the paracortex
What are T cells activated by?
DCs in the paracortex
What happens following activation of T cells? What are fully differentiated Tfh cells able to do?
upregulate CXCR5 and moves towards the high concentration of CXCL13
able to move into the follicle and sustain responses there
How does the first interaction between T and B cells promote Tfh differentiation?
activates ICOS signalling on T cells which induces transcription of Bcl-6 and c-Maf and allows for sustained contacts between B and Tfh cells
What happens during sustained contact between B and Tfh cells?
B cell responses continue and form germinal centres
What do germinal centres develop from and what are they composed of?
develop from primary foci and are composed of mainly rapidly proliferating B cells
What can germinal centres be divided into?
the mantle zone, dark zone and light zone
What is the role of germinal centres?
site for class switching and somatic hypermutation
What do dark zones of germinal centres contain?
centroblasts
high proliferation
What do light zones of germinal centres contain?
centrocytes
lower proliferation but has higher levels of surface Ig
What are plasmablasts and where are they found?
short lived antibody secreting cells which are found in primary foci shortly after B and T cell interaction
What is the role of plasma cells?
can migrate into the bone marrow and become long-lived antibody secreting cells
What is the role of memory B cells?
long lived cells capable of rapid responses following reencounter
What do V(D)J rearrangements during B cell development provide?
diversity and generates closely related clones that are independent of recombination
What is the role of somatic hypermutation?
allows B cells to mutate the genes that they use to produce antibodies
this enables B cells to produce antibodies that are better able to bind to bacteria, viruses and other infections
What is antibody specificity defined by?
the variable region
What is the role of the constant region?
dictates the effector function of an antibody
What does T cell help with CD40L allow B cells to do?
to use different constant regions of the heavy chain and this generally increases the effectiveness following class switching
