Multiple, conserved cryptic recombination signals in VH gene segments: Detection of cleavage products only in pro-B cells

Marco Davila, Feifei Liu, Lindsay G. Cowell, Anne E. Lieberman, Emily Heikamp, Anjali Patel, Garnett Kelsoe

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Receptor editing is believed to play the major role in purging newly formed B cell compartments of autoreactivity by the induction of secondary V(D)J rearrangements. In the process of immunoglobulin heavy (H) chain editing, these secondary rearrangements are mediated by direct VH-to-JH joining or cryptic recombination signals (cRSs) within VH gene segments. Using a statistical model of RS, we have identified potential cRSs within VH gene segments at conserved sites flanking complementarity-determining regions 1 and 2. These cRSs are active in extrachromosomal recombination assays and cleaved during normal B cell development. Cleavage of multiple VH cRSs was observed in the bone marrow of C57BL/6 and RAG2:GFP and μMT congenic animals, and we determined that cRS cleavage efficiencies are 30-50-fold lower than a physiological RS. cRS signal ends are abundant in pro-B cells, including those recovered from μMT mice, but undetectable in pre- or immature B cells. Thus, VH cRS cleavage regularly occurs before the generation of functional preBCR and BCR. Conservation of cRSs distal from the 3′ end of VH gene segments suggests a function for these cryptic signals other than VH gene replacement. JEM

Original languageEnglish (US)
Pages (from-to)3195-3208
Number of pages14
JournalJournal of Experimental Medicine
Volume204
Issue number13
DOIs
Publication statusPublished - Dec 24 2007

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ASJC Scopus subject areas

  • Immunology

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