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The key discovery--one totally unprecedented--was that multiple combinations of gene segments are assembled to form the final antibody gene. The precursors of antibody-producing B cells are continually produced from the bone marrow, and in the process of B cell development, the antibody genes are rearranged to generate novel specificities.
Once antibody genes began to be sequenced, it became apparent that large numbers of genes was not the answer.
By comparing DNA sequences of germline, unrearranged DNA with the sequences of rearranged antibody genes, it became clear that there were three distinct types of gene segments that combined to encode the antigen-binding part of the antibody heavy and light chain genes.
For completeness, I should mention one other mechanism that introduces diversification of antibodies through continued, targeted mutation within the rearranged antibody genes. This happens when clones of stimulated B cells are rapidly dividing in the immune organs such as the spleen and lymph nodes.
I think it is this second type of randomness that occurs in V(D)J recombination in antibody genes. For example, first one particular V region joins to a particular J region, and in the process, the hairpin loop of DNA then happens to be opened at one particular position, followed by the insertion of, say, six nucleotides, each of which could be A, C, G, or T.
I believe and trust that God is at work in the world, and not distant, faithfully bringing about his ultimate aims, while, at the same time, allowing raindrops, lightning bolts, and antibody genes to operate with their own economy, under his all-knowing care and ultimate authority.
An example from my own field of immunology is the process whereby antibody gene segments rearrange to form functional genes, which I will describe below in some detail.
It is quite likely that the antibody gene shuffling processes described below are not actually random in the mathematical sense, since some rearrangements may occur more than others.
In the antibody gene rearrangement system, widely separated segments of DNA join together in unpredictable ways, forming functional genes capable of producing antibody proteins that bind to the surfaces of invading pathogens.
Then they develop a library of the antibody genes in bacterial cells, each gene coding for just one of the antibodies elicited by an antigen.
In the human genome, rearrangement of antibody genes can enable the immune system to target infection more effectively.
Larry Steinman of Stanford University, who is working on a way to put human and mouse antibody genes into bacteria so that the bacteria produce a "hybrid" antibody, says the all-human approach could prove better than the hybrid approach if it works for other proteins besides the two tested.