A NOVEL VH TO VHDJH JOINING MECHANISM IN HEAVY-CHAIN-NEGATIVE (NULL) PRE-B-CELLS RESULTS IN HEAVY-CHAIN PRODUCTION

A NOVEL VH TO VHDJH JOINING MECHANISM IN HEAVY-CHAIN-NEGATIVE (NULL) PRE-B-CELLS RESULTS IN HEAVY-CHAIN PRODUCTION
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DOI:
10.1038/322840a0
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发表时间:
1986-08-28
期刊:
影响因子:
64.8
通讯作者:
WIESE, P
WIESE, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
RETH, M;GEHRMANN, P;WIESE, P

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During B-cell development, theVHgenes of immunoglobulin heavy (H) chains are assembled from three different germline components: the variable (VH) segment, the diversity (D) segment and the joining (JH) segment1,2. The joining between two segments involves the recognition of conserved nonamer–heptamer sequences bordering each segment, double-stranded cuts at the heptamer–segment border, and the re-ligation of the two segment ends which have frequently been modified by the deletion and addition of nucleotides3–6. The flexibility of the joint increasesVHDJHvariability. However, it also results in many pre-B cells which do not produce immunoglobulin H chains and have non-functionalVHDJHcomplexes carrying theVHandJHcoding sequences in different reading frames7. We show here that such ‘null cells’ are not dead-end products of the B-cell developmental pathway but can perform a novelVHtoVHDJHjoining using a 5′VHsegment to replace theVHsequence of theVHDJ−Hcomplex. This process can result in the generation of aVHDJ+Hcomplex and the subsequent expression of an immunoglobulin heavy chain.