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132 / Chapter 9 White cells: Lymphocytes
line state. During early differentiation of B cells heptamer - and nonamer - conserved sequences
there is rearrangement of heavy - chain genes so that flanking the various gene segments. Mistakes in
one of the V heavy - chain segments combines with recombinase activity play an important part in
one of the D segments, which has itself already the chromosome translocations of B - or T - cell
combined with one of the J segments. Th us, they malignancy.
form a transcriptionally active gene for the heavy The pattern of gene and protein expression that
chain. The protein coding segments of the C region is seen during B cell development is valuable in
mRNA are joined to the V region after splicing out determining the stage of B cell development and is
intervening RNA. The class of immunoglobulin useful in leukaemia diagnosis (Figs 9.5 and 9.6 ).
that is secreted depends on which of the nine (4 γ ,
2 α , 1 μ , 1 δ and 1 ε ) constant regions is used.
T - c ell r eceptor g ene r earrangements
Diversity is introduced by the variability of
which V segment joins with which D and with The vast majority of T cells contain a TCR com-
which J segment. In the arbitrary example shown posed of a heterodimer of α and β chains. In a
in Fig. 9.4, V 2 joins with D 1 and J 2 . Additional minority of T cells, the TCR is composed of γ and
diversity is generated by the enzyme terminal deox- δ chains. Th e α , β , γ and δ genes of the TCRs each
ynucleotidyl transferase (TdT), which inserts a vari- include V, D, J and C regions. During T - cell ontog-
able number of new bases into the DNA of the D eny, rearrangements of these gene segments occur
region at the time of gene rearrangement. Similar in a similar fashion to those for immunoglobulin
rearrangements occur during generation of the genes, thus creating T cells expressing a wide variety
8
light - chain gene (Fig. 9.5 ). Enzymes called recom- (10 or more) of TCR structures (Fig. 9.6 ). TdT is
binases are needed both in B and T cells to join involved in creating additional diversity and the
up the adjacent pieces of DNA after excision of same recombinase enzymes used in B cells are
intervening sequences. These recognize certain involved in joining up TCR gene segments.
Pro-B Pre-B Early B Mature B
Heavy chain gene rearranged
κ light chain gene rearranged
λ light chain gene rearranged
TdT
HLA-DR
Cytoplasmic
Surface immunoglobin
Figure 9.5 The sequence
CD10 of immunoglobulin gene
rearrangement, antigen and
CD19
immunoglobulin expression during
CD20 early B - cell development.
Intracytoplasmic CD22 is a feature
PAX5
of very early B cells. HLA, human
CD79a leucocyte antigen; TdT, terminal
deoxynucleotidyl transferase.