Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.
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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.
Green Fluorescent Proteins
Immunoglobulin Variable Region
Mice, Inbred C57BL
Molecular Sequence Data
Published Version (Please cite this version)10.1084/jem.20071224
Publication InfoDavila, Marco; Liu, Feifei; Cowell, Lindsay G; Lieberman, Anne E; Heikamp, Emily; Patel, Anjali; & Kelsoe, Garnett (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 https://hdl.handle.net/10161/10905.
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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,