Chapter 12
B-Cell Activation and Differentiation
Dr. Capers
Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 11
B-Cell Generation, Activation,
and Differentiation
Copyright © 2007 by W. H. Freeman and Company
B cell activation
B cell encounters specific antigen
 B cell presents to T helper cell
 Cytokines are released for full B cell
activation
 Proliferation, some of the B cells
become plasma cells
 Some of the B cell clones move to
germinal centers of lymph nodes,
somatic hypermutation can occur
 Class switching occurs

B cell Activation


Thymus-dependent (TD) antigens
 B cell required direct contact with TH cell
 B-2 B cells, majority of B cells
Thymus-independent antigens (TI)
 These antigens activate B cells by pattern recognition
receptors (bacteria that might be in high amount)
 Type I (TI-1) – lipopolysaccharide
 Type 2 (TI-2) – highly repititous molecules (bacterial
flagella)
B cell Activation

Membrane bound
antibody have short
cytoplasmic tails
○ Too short to generate
signal by associating
with tyrosine kinases
and G proteins

Membrane Ig must
be associated with
B-cell receptor
 Ig-α/Ig-β

ITIM
(immunoreceptor
tyrosine inhibitory
motif)
○ Associated with
CD22
○ Functions to
deactivate B cells –
negative regulation
○ Important in
preventing
autoimmunity

TH cells play
essential role in B
cell repsonses

TEM of interaction between B cell and T
cell
Humoral Response – Primary vs Secondary
Hapten-carrier conjugates

Hapten – low molecular weight molecule
that won’t itself induce a humoral
response
 Must be coupled to suitable carrier
In vivo sites for induction of humoral responses
Blood-bourne antigen is filtered by
spleen
 Antigen from tissue spaces filtered by
lymph nodes

○ Antigen either enters alone or with antigen-
transporting cells
- Langerhans cells
- Dendritic cells
○ Encounters antigen-presenting cells
- Dendritic cells
- Macrophages
- Follicular dendritic in follicles and germinal centers
T cells are green and B cells are red

Germinal centers arise within 7-10 days
after initial exposure to thymusdependent antigen in lymph node
○ 3 events in germinal centers
 Affinity maturation
- Result of somatic hypermutation
 Class switching
 Formation of plasma and memory B cells
Cellular events in germinal centers
Dendritic cell presents antigen
to developing B cells to see
which B cells are producing
antibody with high-affinity
for that antigen
Class Switching

Dependent on cytokines to
switch from IgM to other
isotype
 Thymus-dependent
antigens
 Interaction of CD40 on B
cell and CD40L on T cell
 X-linked hyper-M
syndrome
○ TH cells don’t express
CD40L, patients only
produce IgM
 No memory cell
populations, no germinal
centers
Regulation




Humoral and cell-mediated branches must be heavily
regulated
Cytokines play important role
Antigenic competition
 Previous encounter with antigen can render animal
tolerant or may result in formation of memory cells
Presence of antibody can suppress response to antigen
 Some vaccines are given to babies after maternal IgG
(that was transferred across placenta) has left system
 Vaccination before this will prevent proper response
and development of long-lasting memory cells