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

Publication ,  Journal Article
Davila, M; Liu, F; Cowell, LG; Lieberman, AE; Heikamp, E; Patel, A; Kelsoe, G
Published in: J Exp Med
December 24, 2007

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.

Duke Scholars

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

December 24, 2007

Volume

204

Issue

13

Start / End Page

3195 / 3208

Location

United States

Related Subject Headings

  • Software
  • Recombination, Genetic
  • Probability
  • Molecular Sequence Data
  • Models, Genetic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Immunoglobulin Variable Region
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Davila, M., Liu, F., Cowell, L. G., Lieberman, A. E., Heikamp, E., Patel, A., & Kelsoe, G. (2007). Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells. J Exp Med, 204(13), 3195–3208. https://doi.org/10.1084/jem.20071224
Davila, Marco, Feifei Liu, Lindsay G. Cowell, Anne E. Lieberman, Emily Heikamp, Anjali Patel, and Garnett Kelsoe. “Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.J Exp Med 204, no. 13 (December 24, 2007): 3195–3208. https://doi.org/10.1084/jem.20071224.
Davila M, Liu F, Cowell LG, Lieberman AE, Heikamp E, Patel A, et al. Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells. J Exp Med. 2007 Dec 24;204(13):3195–208.
Davila, Marco, et al. “Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.J Exp Med, vol. 204, no. 13, Dec. 2007, pp. 3195–208. Pubmed, doi:10.1084/jem.20071224.
Davila M, Liu F, Cowell LG, Lieberman AE, Heikamp E, Patel A, Kelsoe G. Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells. J Exp Med. 2007 Dec 24;204(13):3195–3208.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

December 24, 2007

Volume

204

Issue

13

Start / End Page

3195 / 3208

Location

United States

Related Subject Headings

  • Software
  • Recombination, Genetic
  • Probability
  • Molecular Sequence Data
  • Models, Genetic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Immunoglobulin Variable Region