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Blood, 16 July 2009, Vol. 114, No. 3, pp. 547-554. Prepublished online as a Blood First Edition Paper on May 28, 2009; DOI 10.1182/blood-2009-03-211763. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2009-03-211763v1 114/3/547    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zaheen, A. Articles by Martin, A. Search for Related Content PubMed PubMed Citation Articles by Zaheen, A. Articles by Martin, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 18, 2009 Accepted May 24, 2009 AID constrains germinal center size by rendering B cells susceptible to apoptosis Ahmad Zaheen, Bryant Boulianne, Jahan-Yar Parsa, Shaliny Ramachandran, Jennifer L. Gommerman, and Alberto Martin* Department of Immunology, University of Toronto, Toronto, ON, Canada * Corresponding author; email: alberto.martin{at}utoronto.ca. The germinal center (GC) is a transient lymphoid tissue microenvironment that fosters T cell-dependent humoral immunity. Within the GC, the B cell-specific enzyme, activation-induced cytidine deaminase (AID), mutates the immunoglobulin locus thereby altering binding affinity for antigen. In the absence of AID, larger GC structures are observed in both humans and mice, but the reason for this phenomenon is unclear. Since significant apoptosis occurs within the GC niche to cull cells that have acquired non-productive mutations, we have examined whether a defect in apoptosis could account for the larger GC structures in the absence of AID. In this report we reveal significantly reduced death of B cells in AID-/- mice as well as in B cells derived from AID-/- bone marrow in mixed bone marrow chimeric mice. Furthermore, AID-expressing B cells show decreased proliferation and survival compared to AID-/- B cells, indicating an AID-mediated effect on cellular viability. The GC is an etiological site for B cell autoimmunity and lymphomagenesis, both of which have been linked to aberrant AID activity. We report a link between AID induced DNA damage and B cell apoptosis that has implications for the development of B cell disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Chelico, P. Pham, J. Petruska, and M. F. Goodman Biochemical Basis of Immunological and Retroviral Responses to DNA-targeted Cytosine Deamination by Activation-induced Cytidine Deaminase and APOBEC3G J. Biol. Chem., October 9, 2009; 284(41): 27761 - 27765. [Abstract] [Full Text] [PDF]

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