Organization and Expression of Immunoglobulin Genes

Organization and Expression of Immunoglobulin Genes
I. Uniqueness of the System

A. The Problem
1. The number of possible antibodies that an
individual can produce is vast. a. Vast is
a good term here. Technically there can't be an
infinite number. b. Estimates range
from 108 to 1011, but frankly no one really knows.
2. Any one antibody-producing plasma cell synthesizes antibodies with one and
only one CDR (complementarity determining region or antigen binding region).
3. Any one antibody-producing plasma cell can make more than one class of
antibodies, each with the same CDR.
B. The Solution
1. Mixing instructions for chains (heavy and light peptides).
2. Mixing instructions for domains within chains: Dryer and Bennet (in 1965).
3. Evidence for gene rearrangement, Tonegawa and Hozumi (1976). A guy named
Tonegawa actually did the work that proved that the genes for both the light and
the heavy chains of the antibodies will change, will be mutated, will be picked
up, cut apart, rearranged, put together in different ways in the course of
development in a developing B-cell.
C. THIS IS A VERY BIG DEAL.
1. Other Systems with Changes to the Germline DNA
1
.
a. Chromosome Diminution
2
. This is a loss that accompanies the decision to
become a somatic as opposed to a germ cell, and does not seem to be involved in
the regulation of genes involving differentiated state.

1
is the line (sequence) of germ cellsthat have genetic material that may be passed to a child. For example, gametes such as
the sperm or the egg are part of the germline. So are the cells that divide to produce the gametes, called gametocytes, the
cells that produce those, called gametogonia, and all the way back to the zygote, the cell from which the individual
developed.Cells that are not in the germline are called somatic cells. clulas cuyo destino celular es dar linajes encargados
de producir clulas reproductivas y, por tanto, de dar continuidad a la vida entre generaciones (lnea germinal) y aquellas
otras que configurarn el resto del organismo (lnea somtica).
2
chromatin diminution (or more properly, chromatin diminution) is a fascinating exception to the general rule of the
constancy of the genome. Moreover, it provides an interesting alternative to differential gene expression. Instead of
repressing genes that are not being used, why not get rid of them altogether? . Chromatin diminution is defined as
chromosomal fragmentation, followed by the elimination of part of the chromosome during mitosis. During embryogenesis,
the elimination of certain chromosomes from cells that form somatic tissues.
b. Gene amplification. There are a number of systems in which cells make extra
copies of particular genes (rRNA for example).
c. McClintock's jumping genes
3
. She thought they were important in
developmental regulation, but they turned out just to be examples of DNA
parasitism.

d. Neuron development. In mice, at least, as neurons in certain regions of the
brain develop, they relax their controls on transposable elements. Such
elements then move around randomly in the nuclei.

2. What Specifically Makes the Adaptive Immune System Unique

a. Differentiation of B (and T) cells involves clipping DNA out of specific
regions of the immunoglobulin genes.

b. The clipping is not precise within those regions.

c. The clipping takes place at different parts of the regions in different cells.

d. The clipping does not take place in regions other than those for immune
proteins.

e. The clipping results in different cells (and their progeny) ultimately having
different versions of the immunoglobulin genes.

3
Un transposn o elemento gentico transponible es una secuencia de ADN que puede
moverse de manera autosuficiente a diferentes partes del genoma de unaclula, un fenmeno
conocido como transposicin. En este proceso, se pueden causar mutaciones y cambio en la
cantidad de ADN del genoma.

f. These site-specific DNA rearrangements are unique to the vertebrate adaptive
immune system.

Antibody gene rearrangement It is the only system that we have that has a control
developmental event that involves the specific cutting out and throwing away of
various pieces of DNA.
Initially, scientists suggested that B cells could generate Ig diversity by
selecting heavy and light chain instructions from a selection of 1000 genes for
each. What led to the current rejection of this hypothesis?
We can produce more than 1 million different antibodies

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Organization and Expression of Immunoglobulin Genes

I. Uniqueness of the System

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