title: AID-/-mus-/- mice are agammaglobulinemic and fail to maintain B220-CD138+ plasma cells.
abstract: The terminal stage of B cell differentiation culminates in the formation of plasma cells (PC), which secrete large quantities of Igs. Despite recent progress in understanding the molecular aspect of PC differentiation and maintenance, the requirement for the synthesis of secretory Igs as a contributing factor has not been explored. To address this issue, we generated activation-induced cytidine deaminase (AID)/secretory mu-chain (mus) double-knockout mice, in which a normally diverse repertoire of B cell receptors is retained, yet B cells are unable to synthesize secretory Igs. These mice possess polyclonal B cells but have no serum Igs. Following immunization in vivo, PCs, identified by CD138 expression and loss of the B220 marker, were starkly reduced in number in spleen and bone marrow of AID(-/-)mus(-/-) agammaglobulinemic mice compared with wild-type mice. Upon mitogenic stimulation in vitro, AID(-/-)mus(-/-) B cells differentiated into plasmablasts to some extent, but showed reduced survival compared with wild-type B cells. We found no evidence that this reduced survival was attributable to accumulation of membrane IgM. Our results indicate that the synthesis of secretory Igs is a requirement for maintenance of B220(-)CD138(+) PCs.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kumazaki
authors.forename: Boaz
authors.initials: B
authors.lastname: Tirosh
authors.forename: René
authors.initials: R
authors.lastname: Maehr
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D003564:Cytidine Deaminase / Q000172:deficiency / Q000276:immunology*; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D053668:Syndecan-1 / Q000276:immunology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D017493:Leukocyte Common Antigens; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase