GENERATION OF ANTIBODY

DIVERSITY
Presented by:
Mohammed Altaf Khan
Roll number: 155
 INTRODUCTION
• Antibodies are antigen(Ag) binding protien present
on Bcell membrane and secreted by plasma cells.
• Antibodies show diversity to bind with various
antigens.
• Human body can make more than 1010 diverse
antibodies
• This diversification of antibody makes our
immunce defense more strong

Epitope
 Theories to explain diversitiy in antibody

1. Germ line theory

• Our germ cells contains a large ccollection of immunoglobulin gene that
produce diverse antibody
2. Somatic variation theory
• Somatic cells conatain immunoglobulin gene, from which large number of
diverse antibody generated by mutation or recombination.
3. Two gene model
• Given by Dreyer and Bennett in 1965
• Two gene encodes a single immunoglobulin heavy or light chain
• One gene is for variable region and other is for constant region
• 100 to 1000s of variable region
• Only one constant region
4. Tonegawa’s -Immunoglobulin
Genes Rearrange
• In 1976, S. Tonegawa and N. Hozumi they gave direct evidence for separate gene
encodes the variable (V) and constant (C)
• The gene segments are rearaanged in the course of Bcell differentiation
• 1987, noble prize
 Generation of antibody diversity

• To date, there are 7 means of antibody

diversification have been identified in
humans
1. Multiple germ-line gene segments
2. Combinatorial V-(D)-J joining
3. Junctional flexibility
4. P-region nucleotide addition (P-addition)
5. N-region nucleotide addition (N-
addition)
6. Somatic hypermutation
7. Combinatorial association of light and
heavy chain

• Mechanism of VJ joining
• Junctional flexibility
• The enormous diversity generated by means of V
J and V(D)J combinations is further augmented by
a phenomenon called junctional flexibility.
• Joining of recombination signal joint called as
signal joint
• Joining of coding sequence called as coding joint
• RSS joining is always precise but coding
sequence joining can be imprecise
• P-nucleotide addition
• During recombination RAG enzyme cuts to
signal sequence (RSS) site and create hairpin
on terminal of coding sequence
• Hairpin cleaved by endonuclease enzyme
• Short single strand at the end of coding
sequence is formed
• Nucleotide added by repair enzyme
• Generates palindromic sequences thats why it
is as called P-nucleotide addition
• This leads to variation in coding sequence
• N-Nucleotide addition
• During D-J and V to D-J joining process when
a hairpin is cleaved, random nucleotide were
added.
• Enzyme terminal deoxynucleotidyl transferase
(TdT)
• It occurs only in VDJ rearrangement that is
heavy chain
• Upto 15 nucleotides can be added at both DJ
and V-DJ joints.
• After addition- VHNDHNJH
• Somatic hypermutation
• It is a point mutation, occurs at
varaible region
• These mutation take place in
germinal centres only
• Occurs at the rate of 105 to 106
• Goal of this process is to produce
high affinity of antibodies
• Mutation is triggered by an enzyme
called activation induced cytidine
deaminase(AID)
• Cytidine is deaminated to uridine
• This mutation occurs at
Complementarity-Determining
Regions(CDR) of variable region
Ways by which
mutations is induced
 REFERENCES

1. Kuby immunology 5th edition

2. Molecular Biology of B Cells, Second Edition 
• https://doi.org/10.1016/C2011-0-08288-1
3. Immunoglobulin somatic hypermutation
Grace Teng et al. Annu Rev Genet. 2007.
Thank you !