title: T cell-independent development and induction of somatic hypermutation in human IgM+ IgD+ CD27+ B cells.
abstract: IgM(+)IgD(+)CD27(+) B cells from peripheral blood have been described as circulating marginal zone B cells. It is still unknown when and where these cells develop. These IgM(+)IgD(+)CD27(+) B cells exhibit somatic hypermutations (SHMs) in their B cell receptors, but the exact nature of the signals leading to induction of these SHMs remains elusive. Here, we show that IgM(+)IgD(+)CD27(+) B cells carrying SHMs are observed during human fetal development. To examine the role of T cells in human IgM(+)IgD(+)CD27(+) B cell development we used an in vivo model in which Rag2(-/-)gamma(C)(-/-) mice were repopulated with human hematopoietic stem cells. Using Rag2(-/-)gamma(C)(-/-) mice on a Nude background, we demonstrated that development and induction of SHMs of human IgM(+)IgD(+)CD27(+) B cells can occur in a T cell-independent manner.
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Ferenc A
authors.initials: FA
authors.lastname: Scheeren
authors.forename: Maho
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Kees
authors.initials: K
authors.lastname: Weijer
authors.forename: Tom
authors.initials: T
authors.lastname: Cupedo
authors.forename: Jörg
authors.initials: J
authors.lastname: Kirberg
authors.forename: Nicolas
authors.initials: N
authors.lastname: Legrand
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D005312:Fetal Blood / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009154:Mutation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis*
chemical_list: D007072:Immunoglobulin D; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7