Diversity is very important in ensuring a sufficient immune response to accommodate the vast number of immune response. This solution describes in detail, with the aid of a diagram, how B cells generate diversity in the antibodies they produce.© BrainMass Inc. brainmass.com December 24, 2021, 8:24 pm ad1c9bdddf
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Antibody diversity derives from the combination of several different factors. The antibody molecule consists of a constant region, a variable region and junction (J) regions. In the germline, these sections are encoded by different exons spread along the chromosome. As a B cell develops, these exons re-arrange to be juxtaposed to one another, forming an intact gene (see attached figure). In the mouse there are 200-500 variable regions from which to choose, and 4 different J regions, resulting in approximately 2000 combinations of V and J regions. In the case of the heavy chain of the immunoglobulin, there is an additional segment, termed the D region, present between the V and J regions, consisting of 15 different segments, increasing the diversity to approximately 30,000 combinations. Additional variability comes from variations in the boundary recombination at V-J or V-D-J junctions. Depending on the exact location of the junction in the nucleic acid, different codons can be generated, giving rise to different amino acids, thereby increasing diversity. Nucleotides can also be inserted during recombination in the N region, between the D and J segments, which again can shift the codon usage and alter the final amino acid sequence. As the heavy chain and light chain of the antibody undergo recombination independently, the combination of these random heavy and light chains also adds to the diversity in the antibody repertoire. After B cell development has occurred, and the B cell encounters antigen, there can be an additional mechanism to increase diversity, called somatic hypermutation. When B cells are activated, and receive help from CD4 T cells, they enter the germinal center, where random mutations can occur in the variable region. While some mutations may weaken the affinity for antigen, others will enhance the affinity, and these are selected during the response, resulting in an increase in the affinity of the antibody produced.
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