Landreth K S, Kincade P W, Lee G, Harrison D E
J Immunol. 1984 Jun;132(6):2724-9.
Mice homozygous for mutations at the dominant spotting or W locus on chromosome 5 have been extensively used as models of severe macrocytic anemia caused by defective hemopoietic stem cells. We examined cells of the developing B lineage in adult and embryonic W anemic mice both by phenotypic analyses and by three distinctly different functional assays for B lymphocyte precursors. Adult W/Wv mice had normal numbers of B cells in the spleen and bone marrow, and normal numbers of pre-B cells and cells identified by a monoclonal antibody directed to a B lineage cell surface antigen (14.8) in the bone marrow. Embryonic W/Wv and Wx/Wx mice had hypoplastic liver development at 16 days gestation with a corresponding reduction in absolute numbers of pre-B cells, 14.8+ cells, and clonable granulocyte-macrophage progenitor cells, although their frequencies were normal. As expected, spleen colony-forming units were greatly reduced both in absolute number and frequency. Adult bone marrow cells and fetal liver cells from W anemic mutants generated B cells in vitro as well as did cells from normal littermates, but W anemic cells failed to generate B lymphocytes as well in vivo. These observations likely reflect differences in precursor cells that contribute to B cell formation in these assays, and suggest that early B lineage precursors are reduced or defective in W anemic mice.
5号染色体上显性斑点或W位点发生突变的纯合子小鼠已被广泛用作造血干细胞缺陷导致的严重大细胞性贫血模型。我们通过表型分析以及针对B淋巴细胞前体的三种截然不同的功能测定法，对成年和胚胎期W贫血小鼠发育中的B细胞系细胞进行了检测。成年W/Wv小鼠脾脏和骨髓中的B细胞数量正常，骨髓中前B细胞以及由针对B细胞系细胞表面抗原（14.8）的单克隆抗体识别的细胞数量也正常。胚胎期W/Wv和Wx/Wx小鼠在妊娠16天时肝脏发育不全，前B细胞、14.8+细胞和可克隆的粒细胞-巨噬细胞祖细胞的绝对数量相应减少，尽管它们的频率正常。正如预期的那样，脾集落形成单位的绝对数量和频率都大大降低。来自W贫血突变体的成年骨髓细胞和胎肝细胞在体外产生B细胞的能力与正常同窝小鼠的细胞相同，但W贫血细胞在体内产生B淋巴细胞的能力较差。这些观察结果可能反映了这些测定中有助于B细胞形成的前体细胞的差异，并表明早期B细胞系前体在W贫血小鼠中减少或存在缺陷。
