B cell generation-activation_and_differentiation

B cell, its generation and maturation in bone marrow, and activation in lymph node

1. B cell
B-cell Generation, Activation

2. B cell development

1.generation of B Cell
2.Activation of B Cell
3.Differentiation of B Cell into Plasma Cell &
Memory Cell
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HSC B - Cell
Plasma Cell
Memory Cell

3. Overview of B-cell Development

4. Where the B – Cell Generation Takes Place?
before birth: yolk sac
fetal liver
fetal bone marrow
after birth: bone marrow

5. B-cell development in bone marrow

7. Bone-Marrow Stromal Cells Are Required for
Maturation of Progenitor B Cells into Precursor B Cells
VLA-4: very late antigen 4
VCAM-1: vascular cell adhesion
molecule 1
SCF: stem-cell factor
direct contact
is required.

8. Ig gene rearrangement

9. B-Cell Activation and Proliferation

10. Activation of B - Cell
Chemokines CXCL13
Receptor CXCR5
B cell activation factor (BAFF) or
BlyS

11. Antigen presentation to follicular B-cell in
lymph node

12. Response of B-cell on the basis of involvement of T-cell
1.T-cell dependent activation
2.T-cell independent activation
•CD4 T
H
•Type B2 cell
•Requires two types of signals-
multivalent ag binds to mIg
provided by activated T cell

•TI -1 antigens – lipopolysaccharide
of gram –ve bacteria
•TI-2 antigens – highly repetitive
antigens

13. Sequence of Events in B-Cell Activation
by a Thymus-Dependent Ag

15. Signal transduction pathways emerging from BCR

16. B-cell Activation, Proliferation and Differentiation
Occur in a Peripheral Lymph Node

17. 3 Important B-cell Differentiation Events
Take Place in Germinal Centers
1. Affinity maturation or somatic hypermutation
2. Class switch
3. Formation of plasma cells and memory cells

18. AID (activation-induced cytidine deaminase)
Mediates Somatic Mutation
AID – an RNA editing enzyme, deaminating
selective cytidine in certain mRNAs,
changing the cytosines into uracils
– modifying DNA by the deamination
of cytosine, resulting in formation of
uracil

19. Somatic hypermutation- mutations outside the germ
line
•Affects the variable region of both heavy and light chain
•Activation induced cytidine deaminase (AID) enzyme for
SHM & CSR
AID mediated SHM

20. Class Switch recombination (CSR)
That causes change in class of heavy chain
AID mediated CSR
•AID deaminates the cytidine residue and the DNA uridine
Glycosylase enzyme removes the uridine molecule by
formation of nicks.
•This creates single strand break at multiple points.
•Mismatch repair converts this single strand break into double
strand break, which upon repairligates various switch regions.

21. Cytokines Affect Proliferation and Class Switching of B Cells
During the Differentiation of B Cells into Plasma Cells

22. Plasma cell formation in germinal center
BLIMP 1 –B lymphocyte induced maturation protein 1
IRF 4 – interferon regulatory factor 4

23. T independent B cell response
•B cell activation without the help from T cell
•Tend to have polyvalent repeating determinents.
•Innate like adaptive response as only IgM type of ab are
secreted.
TI-1 antigens
•Example – bacterial lps
•T1 antigen crosslink with mIgM.
TI-2 antigens
•Example – bacterial capsule
•Multivalent crosslinking array of BCR

25. Thank you