CHAPTER 4 B Lymphocytes and Immuno

Genes
ts'
laboratories
and appeared to be generally true for antibody
heavy

as

wellas

light
chain V-regions.
,l
4.5 why was this result important for understanding
the
work of antibody genes?
First of all, it explained why only B lymphocytes could use antibody genes. Short
V-region
segments separated from each other by thousands of base pairs
of irre-
levant,
meaningless DNA do not form transcription units and
therefore,
be utilized for the production of antibody
V-regions.

Only ""n.rot,
when the individual
segments are
juxtaposed,
can they be transcribed and the v-region
can

be
expressed.
Second, itshowed that there exists an exact mechanism that
creates

the
antibody
diversity. Since only one out of many V segments is
used
for
rear-
rangement
in a given B-cell
clone, and the processes of rearrangement
are

stochas-
tic, then the mere combination of many
diferent individual segments
already
creates many diferent "shapes" of antibody-variable
regions.
4.6 How many of the combinations between individuat
v-
region segments can be made?
It
depends
on the particular v-region locus. There are three types
of

them:

vH,

v*,
and
v1 @ig. a-2). Each cell has two homologous vg, two homologous
v1,

a.ra

two
homologous v1 loci,
one locus per chromosome (all three typis
of

loci

are

mapped
to diferent chromosomes). The light chain
v-region t*i(v.
and

v1)
consist
of two kinds of gene segments: v and J segments. The vg loci
tonsist

oi

three
kinds of segments.
They have, in addition to the v and thi
J

segments, an

additional
kind of segments called D segments (for
'.diversity',)
The
.
number

of

v
.se.grng*nts

in.the

lgman
Vs
locus

(Vs
segments) is known to be
g0
to 100 (depend-
ing

on

the

individual). The number of human D segments is approximateiy
30,
whilst

Js

segments
number six. The number of V* and V1 segments,
as

well

as

the
number
of individual segments in the V-region loci in the
mouse

is

not

exactly

known,
but
good
estimates
have been made. It is generally
thought

that

in

the
human

as

well

as
in the mouse, the V* Iocus has approximaiely
500

individual V*

segments

and
four J* segments.
The v1 locus in the mouse is small
-

it

has

only
two

vl

and

two
Jl segments. In the human, the vllocus is bigger
and

is

thought to
contain approximately
100 V1 and several J1
segments.
As

one

can

see
from these data, there exists a substantial germline
diversity

of V-
region

gene
segments.
When rearrangements begin,
there
ls
a

sizeable

,.starting

material"

available,
so that a variety of diferent
v,D, and J
segments

can

bI

picked
in diferent B-lymphocyte clones. The total number
of

all pissible
combi-
nations

between
the V, the D, and the J segments (termed "combinatorial
diver-
sity")
cannot, according to
simple rules of combinatorics,
be
greater
than

the
product
of multiplication between the three numbers. For ,*a*fI.,
the maximal

number
of combinations
between all the diferent segments in
the

human

Vs

locus
cannot

be gr'eater
than 100 (i.e., the number of individual vg
segments)
,
Io

1tt.

number
of D
segments) x.6 (the number of Js segments)
-
lg,ooo (Fig.
a-2).
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