1.
B-LYMPHOCYTES,
MATURATION,GENERATION AND
ACTIVATION

2.
Introduction
 B lymphocytes have derived their name from the set of the maturation
from Bursa of Fabricus in birds
 B lymphocytes function in the Humoral immunity component of
adaptive Immune system secreting antibody.
 B cells are generally classified into plasmid all which release
antibody and other one is memory cells.

3.
B-Cell development in the bone marrow
B Regulates construction of an antigen receptor
Bone Marrow provides a
MATURATION & DIFFERENTIATION MICROENVIRONMENT
for B cell development
Ensures each cell has only one specificityB
Checks and disposes of self-reactive B cellsB
Exports useful cells to the peripheryB
Provides a site for antibody productionB

4.
B Cell Maturation
 The Antigen-independent maturation of B cells occurring in Bone marrow involves
acquisition of B cell Receptors (BCR’S) costimulatory molecules, signalling molecules , co
receptors.
 The progenitor cells divide to produce Pro B cells ,the pro B cells differentiation is achieved by
the interaction of the progenitor with Bone marrow stromal cells.
 The receptors involved in this interaction are adhesion molecules expressed by both the cell
types stem cell factor expressed on stromal cell and it’s ligand C-kit expressed by Pro B cell.
 The stromal cells secrete cytokine IL-7 which helps in converting Pro B cell into pre B cell.
 The immunoglobulin gene rearrangement takes place at the pro-B stage successful
rearrangement results in the expression of B cell receptor BCR on the surface of B cells.

5.
B CELL RECEPTOR
The B-cell receptor or BCR is a transmembrane receptor protein located
on the outer surface of B cells.
The receptor's binding moiety is composed of a membrane-
bound antibody that, like all antibodies, has a unique and randomly
determined antigen-binding site.
 B cell is activated by its first encounter with an antigen that binds to its
receptor (its "cognate antigen"), the cell proliferates and differentiates to
generate a population of antibody-secreting plasma B cells and memory B
cells.
Function is to mediate internalization for subsequent processing of the
antigen and presentation of peptides to helper T cells.BCR functions are
required for normal antibody production, and defects in BCR signal
transduction may lead to immunodeficiency.

6.
Positive selection of B-Cells
B-cell undergo the positive selection in the bone marrow
In bone marrow the immature B-cells are exposed to thr
variety of self antigen presented by the bone marrow
stromal cells.
B-cells which do not interact strongly with self antigen are
allowed to leave bone marrow

7.
Negative Selection of B Cells
 The immature B lymphocytes expressing membrane IgM do not proliferate and differentiate In response
to antigens in fact, their encounter with antigens in the bone marrow may lead to death on functional
irresponsiveness this property is called negative selection.
 Once the immature B cells encounter the self-antigen, their development is arrested self- antigen that
mediate negative selection are polyvalent and deliver strong signal to IgM expressing a immature B
lymphocytes
 The B-cells try to save themselves by changing or “editing” their receptors by changing the light chains(But
not heavy chains) a phenomenon called receptor editing, in this process RAG(s) reactivated generating an
additional light chain V-J recombination and consequently new immunoglobulin light chain show the
process of receptor editing that occur in B cell.
 The edited light chains together with the original heavy chains is then expressed , these newly edited IgM
expressing a immature B cells usually convert self-reactive in immature B cells into cells that are not self-
reactive thereby rescuing the cells from an otherwise confirmed cell death by negative selection.
 Cells that do not succeeded in replacing the light chains to change their specificity , die.

8.
Development of Pre-B cell from the pro-B cell is a process dependent on bone marrow stromal cells,
stromal cells are non lymphocyte supporting cells of connective tissue of the bone marrow.
Large Pro B cells interact with stromal cell through Adhesion molecules the initial contact between
Pro B cell and stromal cell made via the molecule VLA-4 expressed on Pro B cell membrane and
VCAM-1 expressed on stromal cell membrane.
The initial interaction between VLA-4 and VCAM-1 endorses the attachment of the two cells,
promotes the expression and interaction between C-kit expressed on Pro-B cells and stem cell factor
(SCF) present on stromal cells.
Tyrosine kinase an essential member of the signal transduction pathway , It interaction results with
SCF leads to transmission of signal which results in the activation of IL-7 gene in stromal cells and
expression of IL-7 receptor on the membrane of Pro-B cells.
IL-7 receptor are also expressed on the membranes of Pre-B cells the interaction signals for
proliferation of B cells and rearrangement of Ig genes.
Role of stromal cells in development of B cells

9.
B CELL ACTIVATION

10.
B CELL ACTIVATION
B-cells are activated when antigen binds to receptors on the B-cell
surface, followed by a co-stimulatory signal, usually provided by a
helper T-cell.
Antigens that require co-stimulation by a T-cell to activate a B-cell are
T-dependent antigens and are usually proteins.
 In order for the helper T-cell to stimulate the B-cell both must be
activated - this usually requires that the B-cell internalize the antigen,
process it, and then present it on the cell surface bound to a class II HLA
molecule
The HLA-antigen complex is recognized by a receptor on the surface of
the T-cell (the T-cell receptor, or TCR).

11.
THANK YOU
MADE BY -YASHI JAIN