Human ecology
Translations between biology and sociology
Generation of diversity in B lymphocyte immunoglobulin

In my M.Sc. thesis I listed some methods by which the human immune system generates a diversity of antigen receptors. The specific example I used was the heavy and light chains of B lymphocyte immunoglobulin. However, I did not attempt to relate the methods of generation to their cellular mechanisms.

Golub and Green (1991) describe the methods with which the immune generates a diverse response. Lymphocytes recognise pathogens with antigen receptors. The receptors contain 'heavy' and 'light' protein chains, assembled from three and two gene segments respectively. The heavy chains contain Variable (V), Diverse (D), and Joining (J) segments, the light chains contain just V and J. There are at least six methods in which these genes are used to express diversity: (Taken from Golub and Green (1991) except where noted)

1. Genetic (allelic) diversity - different V,D and J genes in different humans, (Mattila et. al. 1995)
2. Genetic diversity - large numbers of V,D and J genes per organism
3. Recombinatorial - random choice of V(D)J segments expressed in each lymphocyte
4. Junctional - imprecise joining of segments
5. Combinatorial - different V(D)J segments in the heavy and light chain of single lymphocyte.
6. Somatic mutation - lymphocyte replication produces mutation in the V(D)J genes (Brezinschek et. al. 1995).

(From: natural responses to uncertainty)

The following discussion considers only diploid organisms (i.e. those with their chromosomes arranged in pairs).
1. Genetic (allelic) diversity.
Although an individual organism can only have two alleles at each locus, a sexually reproducing population has the potential to maintain more alleles. This is because the two alleles in one organism do not have to be the same as the two alleles in another organism.

If we consider two parent organisms P1 and P2, with alleles (at a given locus L) (A1,A2) and (A3,A4) respectively.

Through the processes of meiotic division and fertilization, each parent passes one allele to each child. Mendel's first law of genetics (the law of segregation) observes that the children of these parents will consist of equal numbers of four genotypes:

(A1,A3), (A1,A4), (A2,A3), (A2,A4)

If organisms with each of these genotypes survive to breed then the four alleles (A1, A2, A3, A4) will be maintained within the population. However, if not all genotypes survive, alleles may be lost with each new generation.

Example: two children survive each round, with no selection effects, and no mutation. (This can be studied with pen, paper, and a random number generator). Monte Carlo result - from 4 alleles to one allele in 13 generations.

As there is a diversity of V, D, and J alleles in the human population, there must be a mechanism that counter-acts this loss of diversity.

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Created 14/7/99