Genetic and Epigenetic Control of V Gene Rearrangement Frequency

T cell receptor V gamma genes rearrange to the J gamma 1 gene segment in a highly ordered fashion during development. We demonstrate a striking correlation between the pattern of expression of unrearranged V gamma genes and the timing of their rearrangement. Thus, the increases in V gamma 2 rearrangements, and decreases in V gamma 3 and V gamma 4 rearrangements observed during development are paralleled by increasing or decreasing levels of the corresponding unrearranged V gene transcript. We also provide evidence that both the V gamma 3 and V gamma 4 genes are accessible in mature V gamma 3+ cells, but that the V gamma 4 gene may be inaccessible in the progenitors of V gamma 3 cells. The results suggest that regulated local accessibility of the chromatin surrounding V gamma genes is responsible for ordered V gamma gene rearrangement during development.

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Immunoglobulin V regions and the B cell

Blood ◽

10.1182/blood.v83.7.1717.bloodjournal8371717 ◽

1994 ◽

Vol 83 (7) ◽

pp. 1717-1730

Author(s):

AK Stewart ◽

RS Schwartz

Keyword(s):

B Cells ◽

B Cell ◽

Negative Selection ◽

Gene Rearrangement ◽

Substantial Evidence ◽

Binding Properties ◽

Immature B Cells ◽

V Genes ◽

V Gene ◽

Gene Restriction

There is now substantial evidence that a small group of V genes predominates in the Ig repertoire of preimmune B cells. This phenomenon of V gene restriction may reflect preferential accessibility of these genes to recombinase, homology-directed V gene rearrangement, promoters and enhances of V gene transcription, or positive and negative selection mediated by the anti-self binding properties of the B cells surface Ig. These mechanisms may operate alone or in combination to influence V gene rearrangement and populations of immature B cells. Although constraints on the pool of rearranged V genes may seem disadvantageous to the immune system, the mechanisms that generate the CDR3s of heavy and light chains ensure extensive diversity in the pre-B- cell population. In mature B cells, somatic mutation of V genes adds further diversity. CDR3 sequences and somatic mutations not only provide potentially useful clonal markers but also help to identify the normal counterparts of malignant B cells.

Download Full-text

Immunoglobulin V regions and the B cell

Blood ◽

10.1182/blood.v83.7.1717.1717 ◽

1994 ◽

Vol 83 (7) ◽

pp. 1717-1730 ◽

Cited By ~ 63

Author(s):

AK Stewart ◽

RS Schwartz

Keyword(s):

B Cells ◽

B Cell ◽

Negative Selection ◽

Gene Rearrangement ◽

Substantial Evidence ◽

Binding Properties ◽

Immature B Cells ◽

V Genes ◽

V Gene ◽

Gene Restriction

Abstract There is now substantial evidence that a small group of V genes predominates in the Ig repertoire of preimmune B cells. This phenomenon of V gene restriction may reflect preferential accessibility of these genes to recombinase, homology-directed V gene rearrangement, promoters and enhances of V gene transcription, or positive and negative selection mediated by the anti-self binding properties of the B cells surface Ig. These mechanisms may operate alone or in combination to influence V gene rearrangement and populations of immature B cells. Although constraints on the pool of rearranged V genes may seem disadvantageous to the immune system, the mechanisms that generate the CDR3s of heavy and light chains ensure extensive diversity in the pre-B- cell population. In mature B cells, somatic mutation of V genes adds further diversity. CDR3 sequences and somatic mutations not only provide potentially useful clonal markers but also help to identify the normal counterparts of malignant B cells.

Download Full-text