1. ASSINGMENT OF IMMUNOLOG
TOPIC
B CELL IMMUNODEFICIENCIES
MADE BY;
MEHTAB HUSSAIN SHAH
B. S MT 3 RD YEAR

2. INTRODUCTION
B cells are lymphocytes that play a large role in the humoral
immune response ( as opposed to the cell- mediated immune response,
which is governed by T cells). The principal functions of B cells are
to make antibodies against antigens, perform the role of Antigen
Presenting Cells ( APCs) and eventually develop into memory B cells
after activation by antigen interaction. B cells are an essential
component of the adaptive immune system
The abbreviation " B", in B cell, comes from the bursa of Fabricius
in birds, where they mature. In mammals, immature B cells are
formed in the bone marrow.

3. Functions
The human body makes millions of different types of B cells each
day that circulate in the blood and lymphatic system performing the
role of immune surveillance. They do not produce antibodies until
they become fully activated. Each B cell has a unique receptor
protein ( referred to as the B cell receptor ( BCR)) on its surface that
will bind to one particular antigen. The BCR is a membrane- bound
immunoglobulin, and it is this molecule that allows the distinction of
B cells from other types of lymphocyte, as well as being the main
protein involved in B cell activation. Once a B cell encounters its
cognate antigen and receives an additional signal from a T helper
cell, it can further differentiate into one of the two types of B cells
listed below ( plasma B cells and memory B cells). The B cell may
either become one of these cell types directly or it may undergo an
intermediate differentiation step, the germinal center reaction, where
the B cell will hypermutate the variable region of its
immunoglobulin gene (" somatic hypermutation") and possibly
undergo class switching.
Activation of B cells
B cell recognition of antigen is not the only element necessary for B
cell activation ( a combination of clonal proliferation and terminal

4. differentiation into plasma cells). B cells that have not been exposed
to antigen, also known as naïve B cells, can be activated in a T cell-
dependent or - independent manner.
T cell- dependent activation
Once a pathogen is ingested by an antigen- presenting cell such as a
macrophage or dendritic cell, the pathogen' s proteins are then
digested to peptides and attached to a class II MHC protein. This
complex is then moved to the outside of the cell membrane. The
macrophage is now activated to deliver multiple signals to a specific
T cell that recognizes the peptide presented. The T cell is then
stimulated to produce autocrines ( Refer to Autocrine signalling),
resulting in the proliferation and differentiation to effector and
memory T cells. Helper T cells ( i. e CD4+ T cells) then activate
specific B cells through a phenomenon known as an Immunological
synapse. Activated B cells subsequently produce antibodies which
assist in inhibiting pathogens until phagocytes ( i. e macrophages,
neutrophils) or the complement system for example clears the host of
the pathogen( s).
Most antigens are T- dependent, meaning T cell help is required for
maximal antibody production. With a T- dependent antigen, the first
signal comes from antigen cross linking the B cell receptor ( BCR)
and the second signal comes from co- stimulation provided by a T
cell. T dependent antigens contain proteins that are presented on B
cell Class II MHC to a special subtype of T cell called a Th2 cell.

5. When a B cell processes and presents the same antigen to the
primed Th cell, the T cell secretes cytokines that activate the B cell.
These cytokines trigger B cell proliferation and differentiation into
plasma cells. Isotype switching to IgG, IgA, and IgE and memory
cell generation occur in response to T- dependent antigens. This
isotype switching is known as Class Switch Recombination ( CSR).
Once this switch has occurred that particular B cell will usually no
longer make the earlier isotypes, IgM or IgD.
T cell- independent activation
Many antigens are T cell- independent in that they can deliver both
of the signals to the B cell. Mice without a thymus ( nude or athymic
mice that do not produce any T cells) can respond to T independent
antigens. Many bacteria have repeating carbohydrate epitopes that
stimulate B cells, by cross- linking the IgM antigen receptors in the
B cell, responding with IgM synthesis in the absence of T cell help.
There are two types of T cell independent activation; Type 1 T cell-
independent ( polyclonal) activation, and type 2 T cell- independent
activation ( in which macrophages present several of the same antigen
in a way that causes cross- linking of antibodies on the surface of B
cells).

6. B cell immunodeficiencies
B cell immunodeficiencies are antibody deficiency disorders that are
restricted to antibody function. Either B lymphocyte development is
impaired, or B cells fail to respond to T cell signals. All or only
selected subsets of immunoglobulins may be deficient. Patients have
recurrent pyogenic infections with encapsulated bacteria. Infections
require early and vigorous treatment with antibiotics and life- long
immunoglobulin replacement therapy.
1. X- linked agammaglobulinemia ( XLA)
2. Hyper- IgM syndrome ( HIM)
3. IgA deficiency
4 Common variable immunodeficiency ( CVID)
5 Other B cell deficiencies
X- linked agammaglobulinemia ( XLA)
X- linked agammaglobulinemia ( XLA) is a typical antibody deficiency
in which production of antibodies is prevented due to a block in B
cell maturation. Serum concentrations of IgG, IgA, and IgM are
markedly reduced. Levels of circulating B cells are significantly
decreased and plasma cells are absent from lymph nodes and bone

7. marrow, although the number of T cells is normal or even
increased. The clinical phenotype may be variable and even
members of the same family can have different symptoms. The
majority of affected boys present with recurrent bacterial infections
from the age of 4 to 12 months following the disappearance of
maternal immunoglobulin. Infections caused by pyogenic bacteria
are the most common clinical manifestations. Rare cases of XLA in
adults.
Hyper- IgM Syndrome
Hyper- IgM syndrome ( HIM) represents a group of distinct entities
characterized by defective normal or elevated IgM in the presence of
diminished IgG and IgA levels. Seventy per cent of the cases are X-
linked in inheritance, and others are autosomal recessive. Male
patients with X- linked hyper- IgM have a history of recurrent
pyogenic infections, and are particularly susceptible to Pneumocystis

8. carinii. They are also prone to profound neutropenia, autoimmune
hemolytic anemia, and thrombocytopenic purpura. Liver disease
including sclerosing holangitis, viral hepatitis as well as hepatic
lymphoma are common and their frequencies increase with age. The
long- term survival rate for patients with XHIM is poor despite
regular use of intravenous immunoglobulins. Less than 30% of the
patients are alive at 25 years of age. Major causes of death include
Pneumocystis carinii pneumonia early in life, liver disease, and
malignancies in later life. Allogeneic bone marrow transplantation or
non- myeloablative bone marrow transplantation from matched,
unrelated donors have been successful in the treatment of hyper-
IgM syndrome.
IgA Deficiency
Selective IgA deficiency is the most common form of
immunodeficiency in the Western world, affecting approximately 1 in
600 individuals. Only about one third of the patients are

9. particularly prone to infections. Most patients have IgA levels below
5 mg/ dl. The serum concentrations of the other immunoglobulins
are usually normal, but patients have a high incidence of
autoantibodies, many with allergies including food reactions, allergic
conjunctivitis, rhinitis, urticaria, atopic eczema, and bronchial
asthma. In about two thirds of the cases, the deficiency does not
lead to an increased occurrence of infections, whereas the remaining
patients suffer from bacterial infections in both the upper and lower
respiratory tract.
Common variable immunodeficiency ( CVID)
Common variable immunodeficiency ( CVID) is a group of
undifferentiated disorders with defective antibody formation. The
incidence is approximately 1:25,000. Patients with CVID usually
have normal number of circulating B cells, but low serum levels of
IgG and IgA. However, the B cells are defective. CVID affects both
females and males equally and it usually has later age of onset than
other antigen IDs. Patients have an unusually high incidence of
lymphoreticular and gastrointestinal malignancies and the incidence

10. of autoimmune disorders is also increased. CVID forms arise from
several different genetic defects.
Other B cell deficiencie
Other B cell deficiencies have been described including, for example
μ heavy chain deficiency; λ 5 surrogate light chain deficiency; and κ
light chain deficiency.