Chapter 11
B-Cell Generation, 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
Development of B cells

In many vertebrates, including humans and
mice, B cells generate in bone marrow
 Antigen-independent phase
 Ig-gene rearrangement to create antigen-specificity

Immature B cell bearing IgM on membrane
leaves bone marrow
 Matures to express both IgM and IgD with single
antigen specificity
 NAÏVE B cells – have not encountered antigen

Encounter antigen in secondary lymphoid
tissue
 Differentiate into plasma cells and memory cells
 Class switching

Bone marrow
 Pro-B cell → precursor
B cell
 Stromal cell in bone
marrow secrete IL-7
that help development
into immature B cells

Pro-B Cell
○ Heavy chain rearrangement

Pre-B cell
○ Light chain rearrangement

Immature B cell
○ Is now committed to antigenic specificity and
produces IgM
○ B cell not fully functional, must first express
both IgM AND IgD on membrane

In mice, 90% of B cells produced
everyday die without ever leaving bone
marrow
○ Negative selection due to cells that express
auto-antibodies against self antigen in the
marrow
B cell Activation

Thymus-dependent (TD) antigens
 B cell required direct contact with TH cell

Thymus-independent antigens (TI)
 These antigens activate B cells by different
means
 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