Question

10) Why are developing T cells so much more likely to successfully recombine TCR beta chain genes than B cells combine Heavy chain genes?

Answer 1

T-cell receptors are structurally similar to immunoglobulins and are encoded by homologous genes. T-cell receptor genes are assembled by somatic recombination from sets of gene segments in the same way as are the immunoglobulin genes. Diversity is distributed differently in immunoglobulins and T-cell receptors; the T-cell receptor loci have roughly the same number of V gene segments but more J gene segments, and there is greater diversification of the junctions between gene segments during gene rearrangement. Moreover, functional T-cell receptors are not known to diversify their V genes after rearrangement through somatic hypermutation. This leads to a T-cell receptor in which the highest diversity is in the central part of the receptor, which contacts the bound peptide fragment of the ligand. But in B cell, DNA segments for both heavy (VDJ) and light (VJ) chains are randomly combined. Each B cell ends up with functional genes for making one light and one heavy chain coding for an antibody as a membrane-bound receptor. Antibody specificity depends on the gene fragments used.