Carlsson L, Candéias S, Staerz U, Keller G
National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Eur J Immunol. 1995 Aug;25(8):2308-17. doi: 10.1002/eji.1830250829.
We have isolated four distinct fetal liver (FL) populations based on the expression of AA4.1 and the low-affinity Fc gamma receptors type II and III (Fc gamma RII/III), and characterized them with respect to B cell, T cell, and myeloid precursor content. Polymerase chain reaction analysis revealed that the prevalent Fc gamma R isoform at this stage of FL development (day 12 of gestation) was Fc gamma RIII. Two of the four populations, one which expressed AA4.1 but little if any Fc gamma RII/III (AA4.1+), and one which expressed abundant levels of both markers (AA4.1+/FcR+), contained B cell precursors that grew and differentiated to generate VHDJH-rearranged B-lineage cells on S-17 stromal cells in the presence of IL-7. When cultured on FLST2 stromal cells only the AA4.1+ cells generated VHDJH-rearranged B-lineage cells. T cell precursors as assayed by their ability to repopulate fetal thymi in organ culture were found only in the AA4.1+ fraction. In contrast to the lymphoid precursors, myeloid precursors able to generate colonies in methyl cellulose cultures were found in all four fractions including the one which expressed Fc gamma RII/III but no AA4.1 (FcR+) and the one which expressed neither marker (AA4.1-/FcR-). The AA4.1+ population which contained both B cell and T cell precursors was enriched for precursors from many myeloid lineages including the most immature ones which generated multilineage colonies. In contrast, the AA4.1+/FcR+ population, which also contained B cell precursors, was almost devoid of myeloid precursors and the few that were detected were committed to the macrophage lineage. The population defined as FcR+ was also enriched for precursors; however, the majority of these were committed to the erythroid, the macrophage and the mast cell lineage. The fourth population which expressed neither marker (AA4.1-/FcR-) was enriched for relatively mature erythroid precursors which were not present in any of the other fractions. Together, these findings demonstrate that fractionation of FL cells on the basis of AA4.1 and Fc gamma RII/III expression distinguishes subpopulations of B cell and myeloid precursors and suggests that the low-affinity Fc gamma RIII could play a role in the development of early hematopoietic cells at this stage of ontogeny.
我们基于AA4.1以及低亲和力Fcγ受体II型和III型（FcγRII/III）的表达，分离出了四个不同的胎肝（FL）细胞群体，并对它们的B细胞、T细胞和髓系前体细胞含量进行了表征。聚合酶链反应分析显示，在FL发育的这个阶段（妊娠第12天），普遍存在的FcγR同种型是FcγRIII。四个群体中的两个群体，一个表达AA4.1但几乎不表达FcγRII/III（AA4.1+），另一个表达两种标志物的水平都很高（AA4.1+/FcR+），它们含有B细胞前体细胞，在IL-7存在的情况下，这些前体细胞能够生长并分化，在S-17基质细胞上产生VHDJH重排的B谱系细胞。当在FLST2基质细胞上培养时，只有AA4.1+细胞能产生VHDJH重排的B谱系细胞。通过在器官培养中重新填充胎胸腺的能力来检测的T细胞前体，仅在AA4.1+组分中被发现。与淋巴样前体不同，能够在甲基纤维素培养物中形成集落的髓系前体在所有四个组分中都有发现，包括表达FcγRII/III但不表达AA4.1的组分（FcR+）和既不表达这两种标志物的组分（AA4.1-/FcR-）。包含B细胞和T细胞前体的AA4.1+群体富含来自许多髓系谱系的前体，包括产生多谱系集落的最不成熟的前体。相比之下，同样包含B细胞前体的AA4.1+/FcR+群体几乎没有髓系前体，检测到的少数髓系前体已定向分化为巨噬细胞谱系。定义为FcR+的群体也富含前体；然而，其中大多数已定向分化为红系、巨噬细胞和肥大细胞谱系。第四个既不表达这两种标志物（AA4.1-/FcR-）的群体富含相对成熟的红系前体，而其他任何组分中都不存在这种前体。总之，这些发现表明，基于AA4.1和FcγRII/III表达对FL细胞进行分级分离，可以区分B细胞和髓系前体的亚群，并表明低亲和力FcγRIII可能在个体发育的这个阶段对早期造血细胞的发育起作用。
