CHAPTER 6

B cell generation, Activation ,

Differentiation ,and Immunoglobulins
B-Cell Maturation
• B-cells arise from progenitor Lymphocytes.

• Generation of mature B cells first occurs in the embryo and

continues throughout life

• The sites including:

• Yolk sac
• Fetal liver
• Fetal bone marrow are the major sites of B-cell maturation.

• After birth maturation continues in the bone marrow.

B cell maturation and activation
• Naïve B cells circulate in
the blood and lymph and
carried to the secondary
lymphoid organs such as
spleen and lymph nodes

• Activation of B cells
results in Ag-dependent
proliferation (clonal
expansion), differentiation
into plasma/memory cells,
affinity maturation and
class switching
B-Cell Maturation continued
• Maturation results divided into three broad
stages:
1. antigen independent maturation of
immunocompetent B cells
2. activation of mature B cells when they interact with
antigen, and
3. differentiation of activated B cells into plasma cells
and memory B cells.
B-Cell Maturation continued
• The antigen independent phase of B-cell
development
• maturation directed by the Bone marrow
• involves orderly, sequential rearrangement of
Ig-gene rearrangements
• progresses in the absence of antigen.
B-Cell Maturation continued

In bone marrow – is antigen independent

B-Cell Maturation continued
• A mature B cell leaves the bone marrow expressing
membrane-bound immunoglobulin (mIgM and
mIgD) with a single antigenic specificity.
• these B cells are educated to respond to specific
antigens, but
• have not encountered the appropriate antigen – are
sometimes referred to as naive
B-Cell Activation and Proliferation
• B cell activation occurs circulation secondary lymphoid

• B cell proliferation and differentiation occurs in

secondary lymphoid organs

• Activation and clonal expansion are driven by

encounter with specific foreign antigen, resulting in
• generation of plasma cells
• Memory (with long life span)
B-Cell Activation and Proliferation
• In the absence of antigen-induced activation,
• naive B cells in the periphery have a short life
span
• they will die if the appropriate antigen is not
encountered
• death, within a few weeks, is by apoptosis
B-Cell Activation and Proliferation continued
• Most antigens are T cell dependent (TD):

• Requires direct contact with TH cells.

• examples of these antigens include proteins, lipoproteins, and
saccharides

• B cells stimulated by these antigens usually produce IgM

and IgG responses
• with antibodies that are found in the circulation for prolonged
time periods

• Activation by this route typically results in Memory B cells

B-Cell Activation and Proliferation continued
T cell-independent (TI) antigens:
• can activate B cells without direct participation
by TH cells .
• this response to TI antigen usually involves
simple lipids
• antibody production is weaker, no memory
cells are formed
• IgM is the predominant antibody secreted
• reflects low level of class switching.
The Humoral Response
• humoral response/activation differs between
• Primary response – initial response from activation of
naive B cells, and
• Secondary response – response by memory B cells,
previously involved in exposure to the antigen.

• both cases lead to production of secreted antibodies

of
• various isotypes and immunoglobulin classes.
• variable onset of response and amount of antibody
Primary and Secondary Response
 :
Immunoglobulins
Structure and Function
 Antibodies
1. Definition - Molecules that are
produced by the body in
response to a foreign substance
and are antagonist to it.
2. They are known as
Immunoglobulins when not
referring to their specificity
3. Immunoglobulins reside in the
globulin fraction of serum.
Five Immunoglobulin Classes;
IgG, IgA, IgM, IgD, & IgE

Fab, Disulphide bonds

Hinge, Domains, Variable regions,
Constant regions, COOH end,
NH3 end, Binding site
Antibodies
1. Properties
• C’ Fixation
• Placental transfer
IgG
• Characteristics
• 150,000 MW
• Highest serum conc.
• Transported across
placenta via Fc –
• relevant to Lab
diagnosis of ID,
Laboratory false positive
serologies
• Four subclasses (IgG1-4)
• Monomeric in form
IgA
Characteristics
• Dimer, monomer
• Secretions
• Tears, Saliva, GI tract, Colostrum
• Secretory IgA has Secretory component made by
epithelial cells, that protects it from enzymatic and
other chemical degradation
• It prevents viral and some bacterial attachment to
mucosal epithelial cells
• Dimeric form has J chain - connects
IgM

• Characteristics
• Pentameric form

• Primary response
• Role in Lab Diagnostics

• Does not pass placenta

• Effective agglutinator

• Most efficient C’ fixation

IgE
• Characteristics
• Extra Constant region domain (C4)
• Lowest serum concentration
(meaning to diagnostic Lab tests)
• Binds to Mast cells via Fc - Allergic
reactions
• Protection - Parasitic infections
IgD
• Low concentration in serum (<1%)

• Function largely unknown - may act as Antigen

receptor for B cells

• No clinical need to measure - clue to physician

competence & clerical error
Antibody - Antigen Interactions
• Antibody binding site
• Folded structure - forming cleft
between Heavy and Light chains -
tertiary
• Apple analogy - best fit

• Antigen binding site

• Quite small (6 amino acids)
• Epitope
Outcomes to Antibody Binding
1. Agglutinates Ag (viral,
toxin, protein.)
2. Initiates immune
response
1. Cellular
2. Humoral
3. Activates Complement
4. Cleared/Killed by
phagocytic system