B lymphocytes develop from progenitor cells in the bone marrow, where they undergo gene rearrangement to produce B cell receptors (BCRs) on their surface. Immature B cells that recognize self-antigens undergo receptor editing or apoptosis to eliminate self-reactivity. Stromal cells in the bone marrow secrete cytokines like IL-7 that signal to pro-B cells to differentiate into pre-B cells. Mature B cells leave the bone marrow and circulate in peripheral tissues, where they can be activated by binding of antigen to their BCR along with co-stimulation from helper T cells. Activated B cells proliferate and differentiate into plasma cells that secrete antibodies.

1. SAREER AHMAD KHAN
ROLL NO 307

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 bone
marrow
 Regulates construction of an antigen
receptor
 Ensures each cell has only one specificity
 Checks and disposes of self-reactive B
cells
 Provides a site for antibody production
 Exports useful cells to the periphery

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

5.  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

6. 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

7.  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

8. 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 the 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

9. 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

10.  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

11.  Cells that do not succeeded in replacing
the light chains to change their specificity ,
die

12. Role of stromal cells in
development of B-cells
 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

13.  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

14.  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

15. 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

16.  The HLA-antigen complex is recognized by
a receptor on the surface of the T-cell (the
T-cell receptor, or TCR)