B-cell Development

1
B-cell Development and Activation Chapter 5
Self-Test Questions Sections A, B C
all (section D covered previously)
2
What are the 2 phases of B-cell
development? Antigen-Independent (Maturation)
-- mostly in bone marrow vs Antigen-dependent
(Activation) -- mainly in periphery Antigen-Inde
pendent (Maturation) 1) Pro-B stages --
B-cell markers 2) Pre B-stages -- H- an L-
chain loci rearrangements 3) Immature
B-cell -- functional BCR -- but Is it
safe?
3
How are self-tolerant B-cell selected? Screenin
g on bone marrow stromal cells 2nd chance --
Receptor editing -- mainly LC -- alternative V
segments Survival signals (lt10) or
apoptosis
4
What happens during T-cell dependent B-cell
activation? Td antigens 1) Antigen
crosslinking of antibodies -- antigen
engagement -- Iga/Igß signalling 2) TH cell
engagement -- cell/cell interactions -- MHC
presentation -- TCR recognition -- CD40/CD40L
coupling 3) Cytokine stimulation -- IL4, IL2,
etc. -- class switching to IgG -- memory cell
formation Why so complicated?
5
B-cell activation can occur without T-cell
help Types of B-cell antigens Ti-1 bind to
CD-40 -- have mitogenic activity -- e.g.,
LPS Ti-2 crosslink Abs -- repetitive,
polymeric structure -- e.g. capsule
polysaccharides
Yield only IgM only Short-lived B-cells No
memory cells See Table 5-1
6
Revisiting the lymph node Development of 1O to
2O follicles With germinal centers What
happens in GC? -- affinity maturation
via somatic hypermutation -- memory cells
produced -- class switching
7
How does affinity maturation occur? Key role of
AID -- Activation-Induced Cytidine Deaminase --
induced DNA repair Several rounds of
selection -- long-lived B-cells 1000 X
Increased AG affinity
Bind or Die!
8
How does class switching occur? Alternative RNA
processing and . . . IgM and IgD Secreted
IgM Gene splicing and switch to IgG, IgE, and
IgA Cytokines influence class switching
9
The humoral 1O vs 2O responses What are the key
differences? . . . in lag . . . in magnitude .
. . in isotypes How do properties of memory
cells account for this? In peripheral
tissues Other isotypes in BCR Higher affinity
Ab Greater of cells against AG More rapid TH
cell stimulation More rapid class switch
10
Fc Receptors and antibody effector functions What
does Fc?RII mean? Some example FcR mediated
functions
11
B-cell malignancies can involve different stages
of B-cells Types of lymphocyte malignancies
Myeloma Leukemia lymphoma Chronic vs
acute Clinical Diagnosis 1) Microscopy 2) gel
electrophoresis of serum proteins