Abstract
We employed the B-Indu-Rag1 model in which the coding exon of recombination-activating gene 1 (Rag1) is inactivated by inversion. It is flanked by inverted loxP sites. Accordingly, B cell development is stopped at the pro/pre B-I cell precursor stage. A B cell-specific Cre recombinase fused to a mutated estrogen receptor allows the induction of RAG1 function and B cell development by application of Tamoxifen. Since Rag1 function is recovered in a non-self-renewing precursor cell, only single waves of development can be induced. Using this system, we could determine that B cells minimally require 5 days to undergo development from pro/preB-I cells to the large and 6 days to the small preB-II cell stage. First immature transitional (T) 1 and T2 B cells could be detected in the bone marrow at day 6 and day 7, respectively, while their appearance in the spleen took one additional day. We also tested a contribution of adult bone marrow to the pool of B-1 cells. Sublethally irradiated syngeneic WT mice were adoptively transferred with bone marrow of B-Indu-Rag1 mice and B cell development was induced after 6 weeks. A significant portion of donor derived B-1 cells could be detected in such adult mice. Finally, early VH gene usage was tested after induction of B cell development. During the earliest time points the VH genes proximal to D/J were found to be predominantly rearranged. At later time points, the large family of the most distal VH prevailed.
Highlights
B cells are key players in adaptive immunity
We intended to use the power of the B-Indu-recombination-activating gene 1 (Rag1) mice to establish or to confirm parameters of B cell development in the adult mouse
We estimated the timing that proB/preB-I cells need for their developmental progression to the subsequent stages of the B cell lineage
Summary
B cells are key players in adaptive immunity. They play an important role as innate-like effector cells [1]. Various subpopulations can be defined according to these functions. This is reflected by specific sets of surface markers that are diagnostic for such particular B cell subpopulations. Subpopulations like B-1a, B-2, and marginal zone (MZ) B cells in the spleen and B-1a, B-1b, and B-2 cells in the peritoneal cavity can be distinguished. B cells continuously arise from hematopoietic stem cells (HSCs) that reside mainly in the bone marrow (BM). In the fetus the liver is the major B cell generating organ [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
