VMC 221: Veterinary Immunology and Serology (1+1)

GENETIC BASIS OF ANTIBODY DIVERSITY

• An individual has capacity to produce at least 10⁸ different antibody molecules. Such vast diversity require large number of genes.
• This is impossible as the human DNA molecule contain only 6.6 x 10⁹ nucleotides.
• The genetic information for the synthesis of an immunoglobulin molecule is not present in a continuous array of codons.
• It is present in discontinuous stretches.
• The non-expressed intervening sequences or introns are present between the peptide coding sequences or exons within chromosomal DNA.
• Rearrangements of these sequences taken place during B cell differentiation and antibodies with various specificities are produced.
• Susumu Tonegawa of the Massachusetts Institute of Technology won Nobel Prize in 1987 for his contribution towards understanding the gene arrangement of antibody production.
• Immunoglobulin molecule is mode up of V (variable) domain, C (constant) domain and J (joining) segments.
• V region of L-chain is encoded by V and J gene segments.
• V region of H-chain is encoded by V, D and J gene segments.
• In any particular species the number of C segments is limited and there need to be only one gene or a few genes for each constant region which are transmitted from generation to the generation in the germ line.
• The sequences in V domains are variable and body must produce large numbers of V_L and V_H to produce large diversified antibodies.
• The important theories for the origin of large number of V sequences are
  • Germ line theory
  • Somatic mutation theory