Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.
| dc.contributor.author | Davila, Marco | |
| dc.contributor.author | Liu, Feifei | |
| dc.contributor.author | Cowell, Lindsay G | |
| dc.contributor.author | Lieberman, Anne E | |
| dc.contributor.author | Heikamp, Emily | |
| dc.contributor.author | Patel, Anjali | |
| dc.contributor.author | Kelsoe, Garnett | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2015-11-18T16:42:04Z | |
| dc.date.issued | 2007-12-24 | |
| dc.description.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 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. | |
| dc.identifier | ||
| dc.identifier | jem.20071224 | |
| dc.identifier.eissn | 1540-9538 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Rockefeller University Press | |
| dc.relation.ispartof | J Exp Med | |
| dc.relation.isversionof | 10.1084/jem.20071224 | |
| dc.subject | Amino Acids | |
| dc.subject | Animals | |
| dc.subject | B-Lymphocytes | |
| dc.subject | Base Sequence | |
| dc.subject | DNA-Binding Proteins | |
| dc.subject | Frameshift Mutation | |
| dc.subject | Green Fluorescent Proteins | |
| dc.subject | Homeodomain Proteins | |
| dc.subject | Immunoglobulin Variable Region | |
| dc.subject | Mice | |
| dc.subject | Mice, Inbred C57BL | |
| dc.subject | Mice, Knockout | |
| dc.subject | Models, Genetic | |
| dc.subject | Molecular Sequence Data | |
| dc.subject | Probability | |
| dc.subject | Recombination, Genetic | |
| dc.subject | Software | |
| dc.title | Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells. | |
| dc.type | Journal article | |
| pubs.author-url | ||
| pubs.begin-page | 3195 | |
| pubs.end-page | 3208 | |
| pubs.issue | 13 | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Duke Human Vaccine Institute | |
| pubs.organisational-group | Immunology | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | School of Medicine | |
| pubs.publication-status | Published | |
| pubs.volume | 204 |
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