Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell …

H Gu, I Förster, K Rajewsky - The EMBO journal, 1990 - embopress.org
H Gu, I Förster, K Rajewsky
The EMBO journal, 1990embopress.org
Sequence analysis of rearranged VHDJH genes of B lineage cells from various stages of
ontogeny indicates that short sequence homologies at the breakpoints of recombination
contribute to V region gene assembly. Such homologies are regularly seen at DJH junctions
of neonatal pre‐B cells, most of which do not contain N sequences. In the same cells, but not
at later developmental stages, preferential usage of the JH1 element is observed. After birth,
N sequence insertion increases with time and is always more prominent at the VHD border …
Sequence analysis of rearranged VHDJH genes of B lineage cells from various stages of ontogeny indicates that short sequence homologies at the breakpoints of recombination contribute to V region gene assembly. Such homologies are regularly seen at DJH junctions of neonatal pre‐B cells, most of which do not contain N sequences. In the same cells, but not at later developmental stages, preferential usage of the JH1 element is observed. After birth, N sequence insertion increases with time and is always more prominent at the VHD border than the DJH border. In pre‐B cells from adult animals and in mature B cells, in cases where N sequences were not detectable, sequence homologies at the DJH border were found in only half of the instances. This lower incidence could be due to N sequence addition to one of the recombining DNA ends and/or cellular selection. Inspection of VHDJH junctions for N sequence insertion, sequence homologies at the DJH border and JH1 usage allows the estimation of the timepoint in ontogeny at which particular B cell subsets are seeded into the immune system. Specifically, the present data show that the cells of the Ly1 B cell subset are generated not only neonatally but also beyond the first weeks of life. However, the DJH junctions of the progenitors of chronic B cell leukemias which originate from the same B cell subset resemble those of neonatal pre‐B cells, suggesting that these cells have already undergone a transforming event at this early developmental stage.
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