C H A P T E R 3 5 , F IG U R E 2 0

Immunoglobulin heavy chain gene structure and gene processing. Exons of the

heavy chain genes that encode the variable regions of the immunoglobulin molecule are shown in orange. Selection

from these V exons during embryonic development produces the unique sequences of each B-cell clone. The germline

genes for the immunoglobulin heavy chains contain an additional group of exons, the D (diversity, light blue) exons.

Recombination between the V and D regions occurs more frequently than that between the V and J exons in the light

chain exons. Introns between the V and D and between the D and J exons contain signal sequences that regulate the

expression of the enzyme recombinase. This enzyme is responsible for the efficient recombination that gives rise to

the epitope-specific B-cell clones with their individual Ig genes. The heavy chain genes contain exons that encode all

of the isotype heavy chains. Class switching, i.e., the change in chain expression that occurs during antibody synthesis

after B-cell activation, results from alternative splicing between the J exons and the exons for the various heavy chain

isotypes.

C H A P T E R 3 5 , F IG U R E 2 1

Structures for the immunosuppresant, FK506 (tacrolimus). Tacrolimus is a

macrolide isolated from

S trep to m yces tsu ku b a en sis.

Shown from left to right in approximately the same orientation

are the simple line structure, a stick-structure, and a space-filling structure. The stick and space-filling structures are

based on the 3-dimensional structure of the molecule bound to the immunophilin FKBP. Protein data bank designa-

tion 1FKF.