IMMUNOGLOBULIN GENES

Organization of genes

•       Each chain (heavy and light) is encoded by a gene complex

•       Within the gene complex are groups of genes (segments) that encode: V, C, J, D genes                                                               

•       These genes are known by capital letters V, C, J or  D, suffixed by the name of the chain and a number e.g. Vk 3,  Jλ2, Cλ6, Cλ1  (light chain) e.t.c

 

•       Variable region (V genes)

•       Joining genes (J genes)

•       Diversity (D genes)

•       Constant regions (C genes)



 

Light chain - kappa  chain

Gene segments in kappa  chain  -located on chromosome 2

v  250 vk gene segments,

v  4 Jk segments and

v   one ck segment

Potential Diversity for 250*4*1 = 1000

1000 different combinations of genes  in k light chains.

 

 

Light chain germline

The Lambda (λ) chain gene segment : on chromosome 22

v  30  Vλ,

v   5Cλ

Each C gene accompanied by its own J λ gene.

 The potential diversity in the λ genes is therefore

30×5 = 150 different light chains

Heavy chain

•       Human heavy chains are on chromosome 14, have a similar basic structure to the light chain with 2 differences

  1.  Additional diversity- a small no. of diversity (D) gene segments.

2. The different constant region gene segments encoding heavy chain genes (Cγ1-4), Cα1-2, Cμ, Cδ, Cε), are located  together, downstream from VH,  DH,  JH  segments, rather than on separate chromosomes

•       VH gene segments fall into ~  8 families, each with numerous members (some are pseudogenes),

•       Functional VH genes is estimated at 250 – 1000

•       ≈ 12 DH

•        4JH gene segments.

•       The maximum diversity achievable from these range of genes is therefore 1000 × 12 × 4 = 48,000

•       When combined by k light chain e.g, the total potential diversity of molecular structure is an Ig molecule 1000 ×48,000 = 48 million.

•       Alternatively would be combined with λ chain hence additional potential diversity is 150 × 48,000 = 7.2 million – making a combined range of 55.2 million potential molecules

•       This process of forming different antibody specificities through combining different genes randomly is termed combinational diversity.

 

•       Class Switch

•       When sIgM on a B-cell binds to a specific antigen, the B – cell becomes activated , the results  of the activation is transformation into a B cell with surface IgG, IgA or IgE as an alternative for IgM.

•       This is called class switching; this process should occur without the B cell changing its antigen – specificity.

 

Junctional diversity.

•       A no. of nucleotides are often lost or added from the ends of recombining genes segments randomly.

•       Deliberate imprecision  joining of:

•       DH + JH ,

•       VH    to   DHJH

•       VL   to   JL   segments.

•       imprecise joining of gene segments,

•        increases  the diversity of the V – regions

•       This random gain or loss of nucleotides at joining  sites is junctional diversity

•       3 nucleotides  - are required per amino acid, loss or retention of whole codons.

 

Somatic hyper mutation

v  Parts of the variable region of  different antibodies (Ig genes) differed by  a single amino acid (cytosine to uracil in DNA) residue or a single nucleotide sequence from the version of that gene encoded in the  germline (non-rearranged DNA).

v  Such difference appeared after antigenic stimulation and therefore after initial gene rearrangements occurring in that cell

•       Could be during class switching between primary and secondary responses

•        Involves

•       – substitution

•       -   additional of single nucleotide                                         

•        -  deletion       

 

 

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