8536d_ch05_105-136 8/22/02 2: 47 PM Page 112 mac46 mac46: 1256_deh: 8536d: Goldsby et al./Immunology 5e 112 PART I Generation of B-Cell and T-Cell Response RNA then exits from the nucleus. The light-chain mRNa starting from the 5 end: a short L exon, an intron,a binds to ribosomes and is translated into the light-chain pro- VDJ segment, another intron, and a series of C gene seg tein. The leader sequence at the amino terminus pulls the ments. As with the light-chain genes, a promoter sequence is growing polypeptide chain into the lumen of the rough en- located a short distance upstream from each heavy-chain doplasmic reticulum and is then cleaved, so it is not present leader sequence in the finished light-chain protein product. Once heavy-chain gene rearrangement is accomplished, RNA polymerase can bind to the promoter sequence and Heavy- Chain DNA Undergoes transcribe the entire heavy-chain gene, including the introns V-D-/Rearrangements Initially, both Cu and Ca gene segments are transcribed Dif- ferential polyadenylation and RNA splicing remove the in Generation of a functional immunoglobulin heavy-chain trons and process the primary transcript to generate mRNA gene requires two separate rearrangement events within the including either the CH or the Cs transcript. These two variable region. As illustrated in Figure 5-5, a DH gene seg- mRNAs are then translated, and the leader peptide of the re- ment first joins to a JH segment; the resulting DHJH segment sulting nascent polypeptide is cleaved, generating finished p then moves next to and joins a VH segment to generate a and 8 chains. The production of two different heavy-chain VHDHH unit that encodes the entire variable region. In mRNAs allows a mature, immunocompetent B cell to express a rearranged gene consisting of the following sequences, surface. and lgD with identical antigenic specificity on its heavy-chain DNA, variable-region rearrangement produces both IgM Germ-lin H-chain 一高凸 Primary RNA transcript Polyadenylation LVDJ CH L VDJ C5 L V DJ L V DJ C5 u heavy chain 8 heavy chain FICURE 5-5 Heavy-chain gene rearrangement and RNA process. genes, although generally similar to expression of light-chain genes. ing events required to generate finished u or 8 heavy-chain protein. involves differential RNA processing, which generates several differ Two DNA joinings are necessary to generate a functional heavy-chain ent products, including u or 8 heavy chains. Each C gene is drawn as ene: a DH to JH joining and a VH to DHlh joining In this example, a single coding sequence; in reality, each is organized as a series of VH21, DH7, and JH3 are joined. Expression of functional heavy-chai ons and intronsRNA then exits from the nucleus. The light-chain mRNA binds to ribosomes and is translated into the light-chain pro￾tein. The leader sequence at the amino terminus pulls the growing polypeptide chain into the lumen of the rough en￾doplasmic reticulum and is then cleaved, so it is not present in the finished light-chain protein product. Heavy-Chain DNA Undergoes V-D-J Rearrangements Generation of a functional immunoglobulin heavy-chain gene requires two separate rearrangement events within the variable region. As illustrated in Figure 5-5, a DH gene seg￾ment first joins to a JH segment; the resulting DHJH segment then moves next to and joins a VH segment to generate a VHDHJH unit that encodes the entire variable region. In heavy-chain DNA, variable-region rearrangement produces a rearranged gene consisting of the following sequences, starting from the 5 end: a short L exon, an intron, a joined VDJ segment, another intron, and a series of C gene seg￾ments. As with the light-chain genes, a promoter sequence is located a short distance upstream from each heavy-chain leader sequence. Once heavy-chain gene rearrangement is accomplished, RNA polymerase can bind to the promoter sequence and transcribe the entire heavy-chain gene, including the introns. Initially, both C and C gene segments are transcribed. Dif￾ferential polyadenylation and RNA splicing remove the in￾trons and process the primary transcript to generate mRNA including either the C or the C transcript. These two mRNAs are then translated, and the leader peptide of the re￾sulting nascent polypeptide is cleaved, generating finished and  chains. The production of two different heavy-chain mRNAs allows a mature, immunocompetent B cell to express both IgM and IgD with identical antigenic specificity on its surface. 112 PART II Generation of B-Cell and T-Cell Responses FIGURE 5-5 Heavy-chain gene rearrangement and RNA process￾ing events required to generate finished or  heavy-chain protein. Two DNA joinings are necessary to generate a functional heavy-chain gene: a DH to JH joining and a VH to DHJH joining. In this example, VH21, DH7, and JH3 are joined. Expression of functional heavy-chain genes, although generally similar to expression of light-chain genes, involves differential RNA processing, which generates several differ￾ent products, including or  heavy chains. Each C gene is drawn as a single coding sequence; in reality, each is organized as a series of exons and introns. Primary RNA transcript mRNA Nascent polypeptide 5′ Germ-line VH1 VHn DH1 DH7 DH13 JH H-chain DNA D-J joining 5′ Rearranged VH1 VH20 J V DJ H H-chain DNA Transcription V J Polyadenylation RNA splicing D µ heavy chain V J D V J D L L L L L L L 3′ Cµ Cδ Cγ3 Cγ1 Cγ2b Cγ2a Cε Cα 3′ Cµ Cδ Cγ3 Cγ1 Cγ2b Cγ2a Cε Cα Cµ Translation (A)n Cµ Cµ V J D Cδ Translation (A)n V J D Cδ V J D Cδ or or or δ heavy chain 3′ V J D Cµ Cδ 5′ L L L 5′ 3′ VH1 C VH21 DH1 DH6 DH JH µ Cδ Cγ3 Cγ1 Cγ2b Cγ2a Cε Cα V-DJ joining L L L VHn 8536d_ch05_105-136 8/22/02 2:47 PM Page 112 mac46 mac46:1256_des:8536d:Goldsby et al. / Immunology 5e: