T cell-independent development and induction of somatic hypermutation in human IgM+ IgD+ CD27+ B cells.
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.
Scheeren
Ferenc A
FA
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Nagasawa
Maho
M
Weijer
Kees
K
Cupedo
Tom
T
Kirberg
Jörg
J
Legrand
Nicolas
N
Spits
Hergen
H
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*
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7