Open AccessNotch-RBP-J-Independent Marginal Zone B Cell Development in IgH Transgenic Mice with VH Derived from a Natural Polyreactive Antibody
Author(s) -
Zhuo Zhang,
Lei Zhou,
Xinwei Yang,
Yao-Chun Wang,
Ping Zhang,
Lihong Hou,
Xiaoguang Hu,
Ying Xing,
Yufeng Liu,
Wei Li,
Hua Han
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0038894
Subject(s) - marginal zone , b cell , microbiology and biotechnology , biology , transgene , genetically modified mouse , notch signaling pathway , breakpoint cluster region , antibody , antigen , signal transduction , receptor , immunology , genetics , gene
Both the B cell antigen receptor (BCR) signaling and Notch signaling pathway play important roles in marginal zone (MZ) B cell development; however, if and how these two signaling pathways engage in crosstalk with each other remain unclear. In the present study, IgH transgenic mice (TgV H 3B4) were crossed with mice with Notch downstream transcription factor RBP-J floxed alleles (RBP-J f/f ) and Mx-Cre transgene. Subsequently, MZ B cell development was analyzed in 3B4/Cre/RBP-J f/f mice that expressed the transgenic 3B4 IgH and exhibited a deficiency in Notch signaling in B cells upon poly (I:C) injection. We observed that MZ B cell numbers were severely reduced, but still detectable in 3B4/Cre/RBP-J f/f mice, in contrast to increased numbers of MZ B cells in TgV H 3B4 mice and almost no MZ B cells in Cre/RBP-J f/f mice. The majority of the MZ B cells in the 3B4/Cre/RBP-J f/f mice had the same antigen specificity with that of 3B4 antibody, indicating that a particular BCR specificity might direct MZ B cell development in the absence of Notch signaling. The number of MZ B precursor (MZP) cells was reduced sharply in 3B4/Cre/RBP-J f/f mice, and the number of transitional stage 1 and transitional stage 2 cells did not change that much, indicating that the interaction between BCR and Notch signaling likely occurred during the T2-MZP stage. Based on the transgenic mouse model, our data indicate that MZ B cells with certain BCR specificity can develop in a Notch-RBP-J independent manner.