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Chapter 20 B-Cell Development 213

Heavy chain (chromosome 14)
5 3
V 1 V 2 V n D n J 1-6 Enhancer µ δ γ3 γ1 ε2 α1 γ2 γ4 ε1 α2
H
H
H
H
H
Constant region
D J
9 12 7 7 12 9 9 23 7
Signal joint
(degraded)
D J D J
9 12 7 9 12 7 Coding joint
DJ rearrangement
H
5 3
V 1 V 2 V n DJ 1 J 2-6 Enhancer Constant region
H
H
H
H
H
V n D J
H
7 23 9 9 12 7
Signal joint
(degraded)
V n D J
H
V n D J H Coding joint
H
V -DJ rearrangement
H
H
5 3
V DJ 1 J 2-6 Enhancer µ δ Constant region
H
H
H
Transcription
5 3
V DJ 1 J 2-6 Enhancer µ δ
H
H
H
RNA processing
AAA AAA
V D J H1 µ V D J H δ
H
H
Translation and glycosylation Translation and glycosylation
µ Heavy chain protein δ Heavy chain protein
V D J H1 µ V D J H δ
H
H
Fig. 20.2 REARRANGEMENT AND EXPRESSION OF THE HUMAN IMMUNOGLOBULIN HEAVY
CHAIN GENE. The figure shows the Ig heavy chain gene and the signal sequences 3′ of each V region locus,
5′ and 3′ of each D region locus, and 5′ of each J region locus. These consist of heptamer and nonamer
sequences separated by either 12 or 23 base pairs. During immunoglobulin (Ig) recombination, a signal
sequence of 12 base pairs can only join to another of 23 base pairs (the so-called 12–23 rule). As shown in
the figure, initial heavy chain gene rearrangements form coding joints between D and J regions, as well as
signal joints that are ultimately degraded. Subsequently, the joining of the V region gene to the DJ complex
occurs. After a successful rearrangement, the VDJ complex, the µ intron, and portions of the constant regions
are transcribed. RNA processing and differential splicing results in formation of an mRNA molecule that is
then translated. In the example shown, the rearranged VDJ complex and the constant region, with the µ and
δ C region genes, is transcribed. After RNA processing and translation, a particular B cell could then express
µ protein, δ protein, or both.