VHDJH formation and DJH replacement during pre-B differentiation: non-random usage of gene segments.
The Abelson murine leukemia virus (A-MuLV) transformed cell line 300-19 was derived from the bone marrow of an adult NIH/Swiss outbred mouse. The original 300-19 clonal isolate carried DHH rearrangements of both JH alleles, a molecular genotype characteristic of early pre-B cells. During propagation in culture, the 300-19 line frequently generates secondary rearrangements of its JH alleles including rearrangements which append VH segments to the pre-existing DJH complexes to form complete VHDJH variable region genes and secondary D to JH rearrangements which replace the pre-existing DJH rearrangement by joining an upstream D to a downstream JH. The two types of secondary rearrangement events occur at approximately equal frequency. Approximately 30% of the VH to DJH joins lead to the production of mu heavy chains providing support for a regulated model of allelic exclusion. Like pre-B cell lines from other origins, the 300-19 line preferentially utilized VH gene segments from the more JH-proximal (3') families to form VHDJH rearrangements. However, the VH segments preferentially employed by 300-19 were from a different family than those previously demonstrated to be utilized by pre-B lines of BALB/c origin; we relate these different utilization patterns to differences in the organization of the more 3' VH families between the two strains. The initial DJH rearrangements of the 300-19 line employed more 3' (JH-proximal) D segments; however, the DJH replacements preferentially employed the most 5' D segment. We discuss this phenomenon in the context of a mechanism which may target recombinase to regions of the chromosome more 5' to the D locus (VH-containing regions) once an initial DJH complex is formed.
D000011:Abelson murine leukemia virus / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005796:Genes; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region