TY - JOUR
T1 - B-1a Cell Development in Splenectomized Neonatal Mice
AU - Pedersen, Gabriel K.
AU - Li, Xiaohong
AU - Khoenkhoen, Sharesta
AU - Ádori, Monika
AU - Beutler, Bruce
AU - Karlsson Hedestam, Gunilla B.
N1 - Funding Information:
We are grateful to the personnel at the animal facility at the Department of Microbiology, Tumor and Cell Biology at the Karolinska Institutet. This work was supported by the Swedish Research Council (GKH) and David och Astrid Hageléns stiftelse (GKP). The authors have no conflicting financial interests.
Publisher Copyright:
© Copyright © 2018 Pedersen, Li, Khoenkhoen, Ádori, Beutler and Karlsson Hedestam.
PY - 2018/7/30
Y1 - 2018/7/30
N2 - B-1a cells are mainly generated from fetal liver progenitor cells, peri- and neonatally. The developmental steps and anatomical sites required for these cells to become mature B-1a cells remain elusive. We recently described a phenotypically distinct transitional B cell subset in the spleen of neonatal mice that generated B-1a cells when adoptively transferred. This, in combination with findings demonstrating that B-1a cells are lacking in congenitally asplenic mice, led us to hypothesize that the neonatal spleen is required for B-1a cell development. In accordance with previous reports, we found that B-1a cell numbers were reduced in adult mice that had undergone splenectomy compared to after sham surgery. In contrast, neonatal splenectomy led to peritoneal B-1a cell frequencies comparable to those observed in sham-operated mice until 6 weeks after surgery, suggesting that an intact spleen is required for B-1a cell maintenance rather than development. To study the role of the prenatal spleen in generating B-1a cells, we transferred fetal liver cells from pre-splenic embryos [embryonic age 11 (E11) days] into splenectomized recipient mice. B-1a cells were generated in the absence of the spleen, albeit at slightly reduced frequencies, and populated the peritoneal cavity and bone marrow. Lower bone marrow B-1a cell frequencies were also observed both after neonatal and adult splenectomy. These results demonstrated that B-1a cells could be generated in the complete absence of an intact spleen, but that asplenia led to a decline in these cells, suggesting a role of the spleen for maintaining the B-1a compartment.
AB - B-1a cells are mainly generated from fetal liver progenitor cells, peri- and neonatally. The developmental steps and anatomical sites required for these cells to become mature B-1a cells remain elusive. We recently described a phenotypically distinct transitional B cell subset in the spleen of neonatal mice that generated B-1a cells when adoptively transferred. This, in combination with findings demonstrating that B-1a cells are lacking in congenitally asplenic mice, led us to hypothesize that the neonatal spleen is required for B-1a cell development. In accordance with previous reports, we found that B-1a cell numbers were reduced in adult mice that had undergone splenectomy compared to after sham surgery. In contrast, neonatal splenectomy led to peritoneal B-1a cell frequencies comparable to those observed in sham-operated mice until 6 weeks after surgery, suggesting that an intact spleen is required for B-1a cell maintenance rather than development. To study the role of the prenatal spleen in generating B-1a cells, we transferred fetal liver cells from pre-splenic embryos [embryonic age 11 (E11) days] into splenectomized recipient mice. B-1a cells were generated in the absence of the spleen, albeit at slightly reduced frequencies, and populated the peritoneal cavity and bone marrow. Lower bone marrow B-1a cell frequencies were also observed both after neonatal and adult splenectomy. These results demonstrated that B-1a cells could be generated in the complete absence of an intact spleen, but that asplenia led to a decline in these cells, suggesting a role of the spleen for maintaining the B-1a compartment.
KW - B cell progenitors
KW - B-1 cells
KW - fetal liver
KW - splenectomy
KW - transitional B cells
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U2 - 10.3389/fimmu.2018.01738
DO - 10.3389/fimmu.2018.01738
M3 - Article
C2 - 30105023
AN - SCOPUS:85067286826
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1738
ER -