section

35.8

Antibody Diversity andlmmunoglobulin Genes

825

FIGURE 35-18

(Also see color figure.) B-cell clonal selection. Antigen binding to the surface Ig (monomeric IgM and IgD) receptors

occurs only to the B-cell clone that recognizes a particular epitope on the antigen (Figure 35-1).

essentially all of the possible epitopes vertebrate animals

encounter.

Germline immunoglobulin genes consist of exons that

are selected and arranged during differentiation to gen-

erate a mature mRNA. The mRNA is translated to give

an immunoglobulin chain that recognizes a single specific

epitope. The V exons (~ 100) code for the first ~95 amino

acid residues of the variable (VL) regions of the

k

and

X

chains. J (junction) exons code for the next ~15 amino

acid residues. Separate genes exist for the constant (CL)

regions of the

k

and

X

chains. Diversity in the CDR3 region

of the VL chain arises from the various arrangements of the

5 J exons that can occur in combination with any one of the

~ 100 VL exons. The excised DNA of the germline that is

not contained within the final-light chain gene is degraded

leaving a single B-cell DNA structure that “defines” the

particular B-cell clone. The primary RNA transcript that

is formed is spliced such that the primary transcript forms

a mature RNA that is translated to produce the single Ig

light chain. The combinations of V, J, and C exons pro-

duce more than 3000 light chains having different amino

acid sequences. Ig genes can also undergo an “editing”

process during cell division to produce even more spe-

cific antibodies. The processing of the germline genes for

immunoglobulin light chains is shown in Figure 35-19.

Heavy chain genes differ from the light chain genes in

that they include an additional group of DNA segments;

the D (diversity) exons and the genes for the different

FIGURE 35-19

(Also see color figure.) Immunoglobulin light chain gene structure and

gene processing. Germline immunoglobulin genes consist of exons

selected during differentiation to generate the mature mRNA that is

translated to give the immunoglobulin chain that recognizes a single

specific epitope. Exons (>100) code for the first ~95 amino acid residues,

the VL regions of the

k

and A chains. J (junction) exons code for the next

~15 amino acid residues. Separate exons exist for the CL regions of the

k

and A chains. Diversity in the CDR3 region of the VL chain arises from the

various combinations of the 5 J exons that can occur with the ~100 VL

exons. The excised DNA of the germline is degraded, leaving a specific

B-cell DNA that “defines” the particular B-cell clone. The primary RNA

transcript that is formed is spliced such that the primary transcript becomes

a mature mRNA that is translated into a specific Ig light chain.