Antibody diversity

To respond to the enormous variety of antigens that humans and other animals encounter, the immune system must be capable of producing approximately 1015 antigen-specific antibodies. The source of antibody diversity lies in the structure and arrangement of the immunoglobulin genes and the ability of B cells to modify these genes by chromosomal rearrangement. There are three genetic components that encode immunoglobulin. These three components are found on three separate chromosomes and are named as follows: (i) the IGH cluster (named for the heavy chain and located on chromosome 14), (ii) the IGK cluster (named for the kappa light chain and located on chromosome 2), and (iii) the IGL cluster (named for the lambda light chain and located on chromosome 22).

 

The antigen specificity of an antibody molecule depends upon the amino acid sequences in the antigen-binding portions of the heavy and light chain variable domains. The information needed for an immunoglobulin molecule to be produced is coded for in the DNA. The chromosomal light and heavy chain DNA is separated into multiple gene segments that code for the variable (V), joining (J), and constant (C) regions of the light and heavy chains of the antibody molecule and the diversity (D) region of the immunoglobulin heavy chain. The IGK and IGL clusters lack the D segment. Rearrangement of these genes—with one V gene (of which there are approximately 50 functional V segments) recombining with one J gene and one D gene, and together recombining with a C gene—allows for the generation of virtually unlimited antibody diversity from a relatively small pool of chromosomal DNA. In addition, the fully recombined VDJ (heavy chain) and VJ (light chain) genes undergo point mutations (somatic mutation), which can alter the specificity or the affinity of the antibody for the antigen. The process of somatic mutation takes place in the germinal centers of secondary lymphoid tissue, during B-cell proliferation.