Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
UT Southwestern Medical Center, Center for the Genetics of Host Defense, Dallas, TX, United States.
Front Immunol. 2018 Jul 30;9:1738. doi: 10.3389/fimmu.2018.01738. eCollection 2018.
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.
B-1a 细胞主要来源于胎肝祖细胞，围生期和新生儿期。这些细胞成熟为 B-1a 细胞所需的发育步骤和解剖部位仍不清楚。我们最近描述了一种在新生小鼠脾脏中具有独特表型的过渡 B 细胞亚群，当被过继转移时，该亚群可以产生 B-1a 细胞。这与证明先天性无脾小鼠缺乏 B-1a 细胞的发现相结合，使我们假设新生脾脏是 B-1a 细胞发育所必需的。与之前的报告一致，我们发现与假手术相比，接受脾切除术的成年小鼠的 B-1a 细胞数量减少。相比之下，直到手术后 6 周，新生儿脾切除术导致腹膜 B-1a 细胞频率与观察到的假手术小鼠相当，这表明完整的脾脏是维持 B-1a 细胞而不是发育所必需的。为了研究产前脾脏在产生 B-1a 细胞中的作用，我们将来自无脾胚胎（胚胎龄 11 天[E11 天]）的胎肝细胞转移到脾切除的受体小鼠中。尽管频率略有降低，但在没有脾脏的情况下仍产生了 B-1a 细胞，并在腹膜腔和骨髓中定植。在新生儿和成年脾切除后，骨髓中 B-1a 细胞的频率也较低。这些结果表明，B-1a 细胞可以在完全没有完整脾脏的情况下产生，但无脾导致这些细胞数量减少，表明脾脏在维持 B-1a 细胞区室方面发挥作用。
