Molecular genetics of immunoglobulins

At the protein level, antibodies show several types of variability. One is the diversity of the variable (V) regions of heavy (H) and light (L) chains, leading to antibody-combining site specificity; another is the existence of two types of light chain (kappa and lambda); a third is the diversity of heavy chain-constant (CH) regions associated with different effector functions. At the DNA level, V-region variability is coded partly through the large number of VL- and VH-region genes and partly generated by integrating complete V genes from combinations of shorter segments (VL-JL for the light chain, VH-D-JH for the heavy chains), together with somatic mutational events (Tonegawa, 1983). kappa, lambda and H chains are coded independently on different chromosomes and have their own V- and C-region genes (Honjo, 1983). CH-region diversity results from a set of CH genes corresponding to the different Ig subclasses. During B-cell development, rearrangement of DNA occurs both in the VL/VH- and CH-region genes. V-region rearrangements take place at the pre-B-cell stage and produce the complete V-region genes for the heavy and light chains which will permanently characterize an individual clone; CH-region rearrangements enable mature B cells to secrete their V regions on different Ig classes (class switching). This article will review the structure and organization of V and C genes and the control of their expression.