title: Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells.
abstract: 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.
authors.affiliation: Institute for Cancer Genetics, 1150 St Nicholas Avenue, Russ Berrie Science Pavilion, Rm 301, Columbia University, New York, NY 10032, USA. gc87@columbia.edu
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cattoretti
authors.forename: Maike
authors.initials: M
authors.lastname: Büttner
authors.forename: Rita
authors.initials: R
authors.lastname: Shaknovich
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Bachir
authors.initials: B
authors.lastname: Alobeid
authors.forename: Gerald
authors.initials: G
authors.lastname: Niedobitek
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D002467:Cell Nucleus / Q000201:enzymology*; D003564:Cytidine Deaminase / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology; D004789:Enzyme Activation; D006041:Goats; D006801:Humans; D008198:Lymph Nodes / Q000201:enzymology; D051379:Mice; D014066:Palatine Tonsil / Q000201:enzymology; D011817:Rabbits; D051381:Rats; D013154:Spleen / Q000201:enzymology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase