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


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.





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Publication Info

Davila, Marco, Feifei Liu, Lindsay G Cowell, Anne E Lieberman, Emily Heikamp, Anjali Patel and Garnett Kelsoe (2007). Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells. J Exp Med, 204(13). pp. 3195–3208. 10.1084/jem.20071224 Retrieved from

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Garnett H. Kelsoe

James B. Duke Distinguished Professor of Immunology
  1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes.
    2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity.
    3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis.
    4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies.
    5. Mathematical modeling of immune responses, DNA motifs, collaborations in bioinformatics.
    6. Humoral immunity to influenza and HIV-1.

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