Signal sequences govern genome rearragements

Several long segments of chromosomal DNA carrying clusters of v gene

segment, D gene segments, and j gene segments of both mice and humans
have now been sequenced, and the resulting nucleotide pair sequences
suggest the presence of specific v-j, v-d and d- j joining signals. The same signal
sequences are found adjacent to all v gene segment. Similarly. All j gene
segments have identical signal sequences located adjacent to their coding
sequences; however, their signal sequence is different from that adjacent to v
gene segments. Likewise, d and c gene segments have their own adjacent signal
sequences.
Antibody diversity variable joining sites and somatic mutations

How many combinations?

One can readily see that a large amount of diversity can be generated by the
joining of antibody gene segments as just described . for example, consider the
number of different kappa light chains possible in humans: 300 v gene
segmentsx 5 j segments = 1500 fused v j gene segments. The heavy chains
variable region provides even greater diversity because of the multiple D gene
segments. If there are 300 vhgene segments, 25 d gene segments and 6jh gene
segments in human germ line cells, 45000 different heavy chain variable regions
could be assembled. Using these estimates, 67,500,000 different antigen binding
sites could be produced using just kappa light chains. Lambda light chains
produce another level of diversity.
Clearly, these antibody gene segment fusions provide for a vast amount of
antibody diversity. We now know , however that further diversity is generated in
two additional ways. (1) somatic mutation and (2) variability in the sites at which
v-j, v-d, and d-j joining events occur. In total,the possible range of antibody
diversity seems almost limitless.
Regulations a tissue specific enhancer
It has been known for several years that germ line antibody gene are not
transcribed or are transcribed at very low levels. Yet, in antibody producing B
lymphocytes, 10 to 20 percent of the mRNA molecules are antibody gene
transcripts. What, then, is responsible for the activation of transcription of
antibody genes that undergo rearragements and become active? In the case of
the heavy chains gene , the answer appears to be that the rearragement process
brings the promoters located upstream of L11 V11 gene segments into the
range of influence of a strong enhancer element located in the intron between
the jh gene segment and the Chm gene segment (fig 16.10). each LH VH gene
segment contains an upstream promoter. However, prior to the genomic
rearragement events that lead to heavy chain synthesis, this enhancer is over
100,000 nucleotide pairs away from the closer LH-VH promoter. Presumably, this
enhancer cannot activate transcription from promoters that are located that far
away. However, rearragement events occuring during B cell differentiation (see
fig 16.5) move the promoter of the closest LH- VH gene segment to within less
than 2000 nucleotide pairs from the enhancer (fig 16.10, bottom). The enhancer
can now activate transcription from the promoter located upstream from the LH

VH gene segment. The enhancer involved in the activation of heavy chain

synthesis is tissue specific, it activates transcription only in lymphocytes and has
no effect in cells derived from other tissue. Presumably, the activation process
requires the presence of a transcriptional activating factor thatiss synthesized in
lymphocytes, but not in other types of cells.

A similar enhancer element has been found in the intron between the light chain
J gene segment cluster and the C coding sequence. Thus, it seems likely that the
movement of antibody gene promoters into the range of influence of tissue
spesific enhancers may be a general mechanism of

Clonal selection
Kita tidak bisa menghindar tentang pertanyaan yaitu tentang bagaimana
suatu organisme menginisiasi sintesis dari antibodi yang spesific pada
antigentidak bisa sebelum melaluinya . berikut merupakan penjelasan dari clonal
selection theory mengingat pada semua antibodi memproduksi satu lymphocyte
B yang memiliki antigen sama yang terikat secara spesific. Tetapi ada perbedaan
sel yang berada di populasi lymphocyte B yang dapat mengalami perbedaan
urutan genome dari produksi antibodi yang berbeda spesificnya. Populasi dari
limfosit B pada manusia dan tikus akan memproduksi antibodi yang sangat
banyak macamnya.
Allelic exclusion
T cell receptor variability
Major histocompatibility complex