B cell development
Dhruba Acharya
Lecturer/Immunologist
Cells of Immune System
Stem cells of bon marrow
differentiate into
cytokines (IL-&, IL-3)
colony stimulating factor
Lymphoid series Myeloid series
B-lymphocytes T-lymphocytes NK
monocytee-macrophages dendritic cells eosinophils mast cells
General Role of B- and T-Lymphocytes
Stages of Lymphoid Maturation
Lymphocyte maturation
B and T cell are derived from common bone marrow
precursor
Maturation involves the somatic recombination of antigen
receptor gene segments and expression of respective
receptors
The diversity of antibody and TCR repertoires is generated
by the combinatorial association of multiple germline VDJ
and junctional diversity
During B cell maturation, selection process eliminate or
inactivate B cell precursors that express antigen receptor that
are specific for self antigen
Selection process of T cell occurs in Thymus
The antigen with high avidity are negatively selected and
OVERVIEW OF B CELL
DEVELOPMENT
Antigen independent phase of B cell
development
Progenitor B cells proliferates in bone marrow
Ig gene rearrangement produces immature B cells
•First DJ followed by V to DJ rearrangement of Heavy chain
•This forms Pre-B cell
•VJ rearrangement yield light chain formation to form immature
B cell
•Immature B cell express membrane IgM (mIgM) on cell
surface along with Ig-alpha and Ig-beta, thus forming BCR
B-Cell Receptor
BCR Is An Antibody On Surface
Of Cell mIg
Very Short Cytoplasmic Tail,
Cannot Transduce Signal
Heterodimeric Molecule Ig-/Ig-
Transduces (long cytoplasmic tail)
•Immature B cells: only mIgM
•At this stage, B cell is not fully functional, the
engagement of BCR by antigen induces death or
unresponsiveness (anergy)
•Full maturation is signaled by the co-expression of
IgM and IgD
Organization and expression of Ig genes
Heavy chain
Heavy and light chain DNA undergoes V-(D)-J
rearrangement
Self reactive B cells are selected against in bone marrow
Experiment in mouse model
Bone marrow is estimated to produce about 5x107 B cells per
day
Only 10% of it (5x106 cells) recruited into the recirculating B
cell pool.
90 % die either by negative selection or by clonal deletion
Self reactive B cell may be rescued by editing of light chain
gene
OVERVIEW OF B CELL
DEVELOPMENT
Antigen dependent phase of B cell activation
Activation of B cell
Activation of B cell
Antibody response to protein antigen requires CD4
helper T cell (T cell dependent activation)
Antibody response to other than protein doesn’t
require T cell (T cell independent)
Activation of B cell starts with the binding of antigen
with BCR
B cell signaling occurs
Antigen Recognition by the B-Cell-Receptor
An effective signal for B cell activation involves
two distinct signals induced by membrane events
T cell dependent B cell activation
CD40-CD40L interaction stimulate B cell proliferation and differentiation
Activated helper T cell secrete cytokines that along with CD40L, stimulates the
production of antibodies of different isotypes
T cell dependent antibody responses
B cell signaling
X-Linked agammaglobulinemia:
A failure in signal transduction and B cell
development
•Genetically determined immunodeficiency disease
discovered by O.C. Bruton
•Male are affected as X chromosome is involved
•Signs of immunodeficiency appears after one year in
children.
•There is high frequency of infections
•Flow cytometry suggest no mature B cells (few)
Class switching
•Some of the progeny of the B cell that have proliferate in response to T cell and
antigen help differentiate into effecter cells that actively secrete antibodies
•Some of the progeny undergo the process of class switching leading to the
production of antibodies with different isotypes
Molecular mechanism of heavy chain isotype switching
Regulation of B cell activation
Effector mechanism of humoral immunity??????
Thank you!
