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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3967-3975.
Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-10-4170.
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IMMUNOBIOLOGY
Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells
Giorgio Cattoretti,
Maike Büttner,
Rita Shaknovich,
Elisabeth Kremmer,
Bachir Alobeid, and
Gerald Niedobitek
From the Institute for Cancer Genetics, Columbia University, New York, NY; the Department of Pathology, Columbia University Medical Center, New York, NY; the Institute for Pathology, Friedrich Alexander University, Erlangen, Germany; the Department of Pathology, Albert Einstein College of Medicine, Bronx, NY; and the Institute of Molecular Immunology, GSF–National Research Center for Environment and Health, Munich, Germany.
Activation-induced cytidine deaminase (AID) is necessary for immunoglobulin somatic hypermutation (SHM) and class switch recombination (CSR) in T-dependent immune response in germinal centers (GCs). The structural similarity of AID with RNA-editing enzymes and its largely cytoplasmic location have fueled controversial views of its mode of interaction with DNA. We show that AID, a mature B-cell–restricted cytoplasmic antigen, is relocated into the nucleus in 2.5% of CDKN1B–, CCNB1– GC cells. The GC dark zone and the outer zone (OZ), but not the light zone, contain nuclear and cytoplasmic AID+ blasts. AID+ cells in the OZ are in contact with T cells and CD23– follicular dendritic cells. In addition, AID is expressed in extrafollicular large proliferating B cells, 14% of which have nuclear AID. GC and extrafollicular AID+ cells express E47 but not the inhibiting BHLH protein Id2. Outside the GC, AID+ B cells are in contact with T cells and show partial evidence of CD40 plus bcr stimulation-dependent signature (CCL22, JunB, cMYC, CD30) but lack early and late plasma cell markers. The distribution of nuclear AID is consistent with the topography of SHM and CSR inside the GC and in extrafollicular activated B cells.
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