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

Published

Journal Article

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 V(H)-to-J(H) joining or cryptic recombination signals (cRSs) within V(H) gene segments. Using a statistical model of RS, we have identified potential cRSs within V(H) 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 V(H) cRSs was observed in the bone marrow of C57BL/6 and RAG2:GFP and microMT 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 microMT mice, but undetectable in pre- or immature B cells. Thus, V(H) cRS cleavage regularly occurs before the generation of functional preBCR and BCR. Conservation of cRSs distal from the 3' end of V(H) gene segments suggests a function for these cryptic signals other than V(H) gene replacement.

Full Text

Duke Authors

Cited Authors

  • Davila, M; Liu, F; Cowell, LG; Lieberman, AE; Heikamp, E; Patel, A; Kelsoe, G

Published Date

  • December 3, 2007

Published In

Volume / Issue

  • 204 / 13

Start / End Page

  • 3195 - 3208

PubMed ID

  • 18056287

Pubmed Central ID

  • 18056287

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20071224

Language

  • eng