Abstract
The immunoglobulin repertoire is initially generated by the rearrangement of discrete gene segments encoding the heavy and light chains. Heavy chain genes are composed of a variable gene segment (VH), a diversity (D) gene segment and a joining (JH) gene segment, and kappa light chain genes contain variable (VK) and joining (JK) gene segments. In developing B cells, the gene segments are independently selected from pools of several hundred VH and VK gene segments, 12 D gene segments, and four JH or JK gene segments, creating a diverse population of immunoglobulins. The VH gene segments are grouped into nine subfamilies which contain gene segments that share 80% or greater homology, and span a region between 500 and 2500 kilobasepairs (kb) that is located several hundred kb upstream of the D and JH gene segments on chromosome 12 (Brodeur PH, Riblet R, 1984; Brodeur PH, 1987). VK gene segments have been grouped into at least 18 subfamilies and are located upstream of the JK gene segments on chromosome 6 (Potter M, et al, 1982). Addition and deletion of nucleotides at the junctions of the gene segments creates greater diversity in the third hypervariable region in each gene. The repertoire generated by gene rearrangements can be modified by interactions between immunoglobulins expressed on the B-cell surface and endogenous antigens leading to the expansion or inhibition of certain antibody specificities.
Published Version
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