Page 145 - Essential Haematology

Chapter 9 White cells: Lymphocytes / 131

immunoglobulin from a monoclonal population of
Variable antigen
binding site lymphocytes or plasma cells causes paraproteinae-
mia (see p. 273) . Bence - Jones protein found in the
V H V H
Fab V V urine in some cases of myeloma consists of a mono-
fragments L L clonal secretion of light chains or light - chain frag-
C H C H Light chain ments (either κ or λ ). Immunoglobulins may bind
C L C L (κ or λ)
SS to blood cells in a variety of immune disorders and
cause their agglutination (e.g. in cold agglutinin

SS disease; see p. 84 ) or destruction following direct
Papain Papain cleavage
cleavage complement lysis or after elimination by the reticu-
Fc loendothelial system.
fragment

Antigen – r eceptor g ene
a rrangements
Heavy chain
(μ, δ, γ, ε or α) Immunoglobulin g ene r earrangements
Th e immunoglobulin heavy - chain and κ and λ

Figure 9.3 Basic structure of an immunoglobulin
light - chain genes occur on chromosomes 14, 2 and
molecule. Each molecule is made up of two light ( κ or
22, respectively. In the germline state, the heavy -
λ ) (blue areas) and two heavy (purple) chains, and
chain gene consists of separate segments for variable
each chain is made up of variable (V) and constant
(V), diversity (D), joining (J) and constant (C)
(C) portions, the V portions including the antigen -
regions. Each of the V, D and J regions contain a
binding site. The heavy chain ( μ , δ , γ , ε or α ) varies
according to the immunoglobulin class. IgA molecules number ( n ) of diff erent gene segments (Fig. 9.4 ). In
form dimers, while IgM forms a ring of fi ve molecules. cells not committed to immunoglobulin synthesis
Papain cleaves the molecules into an Fc fragment and these gene segments remain in their separate germ-
two Fab fragments.
D J
5' 3'
V1 Vn 1 2 3 n 1 2 3 4 5 6 Cμ
DNA rearrangement
DJ
Rearranged heavy chain
gene DNA V 2 12 3 4 5 6 Cμ
Transcription
RNA splicing

μ mRNA
V DJ Cμ
Translation

Cytoplasmic μ chain
V DJ Cμ

Figure 9.4 Rearrangement of a heavy - chain immunoglobulin gene. One of the V segments is brought into

contact with a D, a J and a C (in this case C μ ) segment, forming an active transcriptional gene from which the
corresponding mRNA is produced. The DJ rearrangement precedes VDJ joining. The class of immunoglobin
depends on which of the nine constant regions (1 μ , 1 δ , 4 γ , 2 α , 1 ε ) is used.