B Cell development,

maturation and activation

N SAKTHIVEL
I M.SC MICROBIOLOGY
23MIC2816
BHARATHIDASAN UNIVERSITY
• B lymphocytes, the cells that produce antibodies, in birds they
were found to mature in an organ called the Bursa of Fabricius. In
mammals, no anatomic equivalent of the bursa exists, and the early
stages of B cell maturation occur in the bone marrow. Thus, B
lymphocytes now refer to bone marrow–derived lymphocytes.

• B cells are found in the germinal centers of the lymph nodes, in the
white pulp of the spleen, and in the MALT.
• B cells perform two important functions:
They differentiate into plasma cells and produce
antibodies.
They can present antigen to helper T cells (Act as Antigen
Presenting Cells).
 In mammals, bone marrow is the site of B cells development. B cell
develop from haematopoietic stem cells.
 The haematopoietic stem cells are present in the medulla of bone
marrow. They are multipotent stem cells. They have the ability of
self renewal.
 These cells gives rise to both myeloid lineage and lymphoid lineage.
 Myeloid lineage : RBC, platelets, monocytes, macrophages,
neutrophils, basophils, eosinophils, dendritic cells etc…,
 Lymphoid lineage : B cell, T cell, NK cells etc..,
 NK cells resemble lymphocytes in morphology. They are rounded
with A large rounded nucleus. The cytoplasm is thin.
 It is process of blood cell deveopment.
 The development of lymphocytes from haematopoietic stem cells is
called lymphooesis.
 The b cells are derived from haematopoietic stem cells. Some of the
haematopoietic stem cells turn into pro-B cells(progenitor B cells).
 The pro-b cells differentiate into pre-B cells(precursor cells).
 Pre-B cells enter the bone marrow and develop into B lymphocytes.
 The B lymphoblast changes into immature B cell which has IgM
molecule on the surface.
 The immature B cell changes into mature B cell which IgD molecules
on the surface in addition to IgM.
 The immature B lymphocytes into the lymph nodes and spleen from
the bone marrow. Here the B lymphocyte is put into action when it is
exposed to antigen.
 When there is proper antigenic stimulation(viruses, bacterial infection
and toxins), the B cells divide rapidly and form two types of daughter
cells, namely plasma cells and B memory cells.
 The plasma cells secrete antibodies in response to specific antigen.
 The memory cells move more actively from blood to lymph. They
survive for a longer time and they respond quickly and effectively
during the subsequent similar antigenic stimulation. They produce
antibodies and thus bring about secondary immune response.
 The B cell are derived from haematopoietic stem cells. Some of
the haematopoietic stem cells turn into pro-B cells.
 The pro-B cells differentiate into pre-B cells.
 Bone marrow stromal cells are necessary to supply correct
environment for pro-B cell to grow.
 B cells initially need direct contact with stromal cells.
 The direct contact is brought about by cell adhesion molecules
such as CD41 present on the pro-B cell and hyalurnic acid present
on the stromal cell.
 After initial contact, the C-kit, of B cell interacts with stem cell
factor of stromal cell.
 This activates C-kit. The pro-B cell begins to divide and
proliferates into the next stage cells called pre-B cells.
 The pre-B cells express IL-7 receptor on their surface.
 The stromal cells secrete IL – 7.
 IL-7 binds to the IL-7 receptor present on the surface of pre-B cells.
 The IL-7 releases the pre-B cell from cell adhesion molecules and
the pre-B cell is detached from stromal cells.

 Pre-B cells enter the bursa of Fabricius and develop into B

lymphoblasts. In mammals this change occurs in the bone marrow
itself.
 The B lymphoblast changes into immature B cell which has IgM
molecule on the surface.
 The immature B lymphocytes move into the lymph nodes and
spleen from the bursa or bone marrow.
 In the secondary lymphoid organs the immature B cell changes into
mature B cell which has IgD molecules on the surface in addition to
IgM.
 In the secondary lymphoid organs, the B-lymphocyte is put into
action when it is exposed to antigen.
 When there is proper antigenic stimulation(viruses, bacterial
infection and toxins), the B cells divide rapidly and form a clone of
B cells. These cells develop into two types, namely plasma cells and
B memory cells. The plasma cells secrete antibodies in response to
specific antigen.
 The memory cells move more actively from blood to lymph. They
survive for a longer time and they respond quickly and effectively
during the subsequent similar antigenic stimulation. They produce
antibodies and thus bring about secondary immune response.
 The immature b cells do not produce antibodies.
 The various steps involved in the proliferation of haematopoietic
stem cells into immature B lymphocyte are independen of antigens.
Hence they are antigen independent processes.
 The proliferation of immature B lymphocytes into plasma cells and
B memory cells is dependent on antigen. So this process is antigen
dependent process.
 The differentiation of b cells into antibody producing cells is
called B cell maturation.
 By maturation, the b cells gain the ability to produce antibodies.
 B cell maturation is an antigen dependent process.
 In the lymphoid organs, virgin b cells are exposed to antigens for
the first time.
 B cells that encounter antigen for the first time are called naïve B
cells.
 The b cells recognize the antigens.
 B cells exist as clones. There are about 10^9 clones of B cells in a
body system. Each clone is specified for a particular antigen.
 A single B cell clone recognizes a particular antigen. Most of the
B cells of that clone differentiate into plasma cells that secrete
antibodies.
 A few activated B cells of that clone become memory B cells.
They recognize the same antigen which encounters in future.
 The activated b cells go through affinity maturation and class
switching.
 With each encounter, the number of memory cells increases. It is
accompanied by affinity maturation which induces the survival of
B cells with great affinity for that antigen.
 Naive b cells have IgM and IgD on their surface.
 They have same binding VDJ regions but different constant
regions.
 They leave the bone marrow with single specificity.
 The naïve b cells have very short life. They live only for 3 days to
8 weeks.
 The activated b cells express receptors for IL-2, IL-4, IL-5 and
others. These bind to cytokines released by T helper cells.
□The pro-B cells develop a B cell marker called B 220 on their
surface. The pre-B cells develop a surrogate light chain on their
surface.

□The immature B cells express on their surface IgM.

□The mature B cells express on their surface both IgM and IgD. The
early stage mature cells, express low levels of IgD. When these cells
reach lymph nodes, the level of IgD increases.

□The activated B cells have IgM, IgD and IgA or IgE. The plasma
cells have on their surface IgG, IgA, IgE or IgM.
 B cell activation
 The process of stimulating the B cells to produce antibodies and
humoral immune response is called B cell activation.
 B cells are bursal or bone marrow derived lymphocytes. They
attack ex- tracellular antigens (bacteria, viruses) by secreting
antibodies. So they bring about humoral immune response.
 B cells are activated by infection or vaccine.
 The activation of B cell begins when the antigen enters the body.
The antigen entering through the tissues reaches the lymph nodes
and that entering through the blood reaches the spleen.
 B cells are activated in two ways. They are: Thymus independent
activation Thymus dependent activation.
 The activation of B cell involves the following events:
 The antigen such as viruses, bacteria, fungus, etc. enter the body
through infection. They reach secondary lymphoid organs. Blood
borne antigens enter spleen. Antigen coming through skin and
epithelia reach lymph nodes. The pathogens inhaled and ingested
reach mucosal lymphoid tissues.
 The non-protein antigens such as polysaccharides, lipids, nucleic
acids etc. are recognized by B cells as well as macrophages. The
B cell gets attached to the polysaccharide antigen. This binding
activates the B cell It is the T cell independent activation as the T
cell is not involved in the activation of B cells.The B cell also
recognizes the antigen present on the macrophage.
 The protein antigen is recognized by B cells as well as antigen
presenting cells (APC) such as dendritic cells, macrophages, etc.
The activation of B cell by the protein antigen requires the help of
T cells. This activation is called T cell dependent activation.
 The B cell or APC gets attached to the antigen.
 The antigen is taken into the cell by endocytosis.
 The antigen is enclosed inside an endosome.
 The antigen is degraded into peptide fragments.
 A peptide fragment is loaded on class II MHC molecule to form
peptide class II MHC complex.
 The peptide-class II MHC complex is deposited on the surface of
the B cell or APC.
 The T helper cell (TH) recognizes this antigen and binds to it.
 The binding of TH cell with the B cell produces a T-B cell
conjugate. The junction between the Th and B cell is called
immunological synapse In the immunological synapse the partner
cells are interconnected by receptor molecules and adhesion
molecules.
 This binding activates TH cell.
 The TH cell secretes autocrines such as interleukin. The
autocrines bind to the same TH cell. The bound autocrines
stimulate the TH cells to proliferate into a clonal of TH cells
containing effector TH cell and memory T cell.
 The TH cells also get activated by making immunological synapse
with dendritic cells and macrophages.
 The effector TH cell secretes paracrines such as cytokines.
 The paracrines activate B cell.
 The activated B cell undergoes proliferation and produces a clone
of B cells.
 The clone of B cell produces two types of cells such as many
plasma cells and a few memory B cells.
 The plasma cells are the effector B cells. They secrete antibodies.
 The antibodies move to the site of infection and get attached to
the pathogen. The antibodies mark the pathogen for killing by
phagocytes and complement system.
 The plasma cells move to the bone marrow and continue secreting
antibodies.
 The antibodies remain circulating in the blood.
 The memory B cells mount a quick response when the same
antigen enters in future.
References
 Immunology by Dulsy fatima, Saras
publications.