Abstract
As B lymphocytes are generated from hematopoietic stem cells, they pass through several intermediate stages that are characterized by distinctive molecular and functional features. The earliest stage is distinguished by accessibility of the immunoglobulin (Ig) heavy chain locus, indicating chromatin changes preparatory to heavy chain rearrangement. Upon activation of the recombinase complex, first a diversity (D) region segment rearranges to one of four joining (J) segments (usually on both chromosomes), and then one of 50–100 variable (V) region genes rearranges to the D-J segment. If this first attempt fails to generate a productive (inframe) heavy chain protein coding sequence, a second V to DJ rearrangement can occur on the other chromosome. Expression of heavy chain protein in the cytoplasm marks the classical pre-B-cell and signals the cell to progress to the next stage of B-cell differentiation—clonal expansion followed by light chain rearrangement. V to J rearrangement at the light chain locus results in expression of a complete IgM molecule, which is rapidly transported to the surface of the immature B-cell. Further differentiation (and possibly selection) finally generates the IgM+IgD+ mature B-cell.
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Hardy, R.R., Shinton, S., Wasserman, R., Li, YS. (1998). Staging B-Cell Development and the Role of Ig Gene Rearrangement in B Lineage Progression. In: Monroe, J.G., Rothenberg, E.V. (eds) Molecular Biology of B-Cell and T-Cell Development. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2778-4_14
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DOI: https://doi.org/10.1007/978-1-4757-2778-4_14
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