Edwards J A, Durant B M, Jones D B, Evans P R, Smith J L
J Immunol. 1986 Jul 15;137(2):490-7.
Frozen sections of human fetal spleen from 12 to 20 wk gestation were examined by using polyclonal antibodies to Ig isotypes, monoclonal antibodies to HLA class II subregion locus products, B and T cells, and follicular dendritic cells. Scattered lymphoid cells in spleen sections from fetuses of 12 to 13 wk gestational age expressed IgM but not IgD. The appearance of lymphoid cells expressing IgD occurred at 14 to 15 wk before the formation of loose clusters of B cells at 16 wk. IgD expression was associated mainly with cells in these clusters, which by 17 wk had become definite follicles. Follicular dendritic cells were not detectable until 20 wk. OKT3-positive T cells were not detected until 17 wk, and at 20 wk constituted 5% of the nucleated cell population. HLA-DR- and DP-positive lymphocytes and macrophages were detectable in fetal spleen from 12 wk onward; DR was expressed on more cells than DP, and the numbers of cells stained by HLA-DR-specific monoclonal antibodies exceeded the number of Ig-positive cells in all spleens examined. HLA-DQ was expressed by consistently fewer cells than HLA-DR and -DP in all spleens tested. The small number of DQ-positive cells in spleens from 12- to 13-wk fetuses had the morphology of macrophages; HLA-DQ expression by lymphoid cells followed a similar pattern to IgD expression and was associated mainly with follicular lymphocytes. It could be demonstrated by double-labeling experiments that all follicular IgM-positive cells in 17- to 20-wk spleens expressed HLA-DP, DQ, and DR antigens: IgM-positive cells in 12- to 16-wk spleens and interfollicular IgM-positive cells in 17- to 20-wk spleens all expressed HLA-DR, but only 59% and 43% expressed DP and DQ, respectively. Ninety-one to 100% of IgD-positive cells in all spleens examined expressed HLA-DQ in addition to DR and DP. In these experiments IgD-negative, DQ-positive cells had the morphologic appearance characteristic of macrophages. These data suggest that class II antigens are differentially expressed on developing lymphoid cells; DR and DP expression occurring in the earliest spleens examined, with expression of DP on a subpopulation of DR-positive cells; IgD and DQ expression appears to be coincident on maturing B cells as they begin to form follicles. An immunoregulatory role for HLA-DQ in B cell development is implicated and remains to be fully investigated.
利用针对免疫球蛋白同种型的多克隆抗体、针对 HLA Ⅱ类亚区基因座产物、B 细胞、T 细胞和滤泡树突状细胞的单克隆抗体，对妊娠 12 至 20 周的人胎儿脾脏冰冻切片进行了检查。妊娠 12 至 13 周胎儿脾脏切片中的散在淋巴细胞表达 IgM 但不表达 IgD。表达 IgD 的淋巴细胞在 14 至 15 周出现，早于 16 周 B 细胞松散聚集的形成。IgD 表达主要与这些聚集中的细胞相关，到 17 周时这些聚集已形成明确的滤泡。直到 20 周才检测到滤泡树突状细胞。直到 17 周才检测到 OKT3 阳性 T 细胞，在 20 周时其占核细胞群体的 5%。从 12 周起在胎儿脾脏中可检测到 HLA-DR 和 DP 阳性淋巴细胞及巨噬细胞；DR 在更多细胞上表达，且在所有检查的脾脏中，被 HLA-DR 特异性单克隆抗体染色的细胞数量超过 Ig 阳性细胞数量。在所有测试的脾脏中，HLA-DQ 表达的细胞始终比 HLA-DR 和 -DP 少。12 至 13 周胎儿脾脏中少量 DQ 阳性细胞具有巨噬细胞的形态；淋巴细胞的 HLA-DQ 表达模式与 IgD 表达相似，主要与滤泡淋巴细胞相关。通过双重标记实验可以证明，17 至 20 周脾脏中所有滤泡 IgM 阳性细胞均表达 HLA-DP、DQ 和 DR 抗原：12 至 16 周脾脏中的 IgM 阳性细胞以及 17 至 20 周脾脏中滤泡间的 IgM 阳性细胞均表达 HLA-DR，但分别只有 59%和 43%表达 DP 和 DQ。在所有检查的脾脏中，91%至 100%的 IgD 阳性细胞除了表达 DR 和 DP 外还表达 HLA-DQ。在这些实验中，IgD 阴性、DQ 阳性细胞具有巨噬细胞的形态学特征。这些数据表明，Ⅱ类抗原在发育中的淋巴细胞上存在差异表达；DR 和 DP 表达出现在最早检查的脾脏中，DP 在 DR 阳性细胞亚群上表达；IgD 和 DQ 表达似乎在成熟 B 细胞开始形成滤泡时同时出现。提示 HLA-DQ 在 B 细胞发育中具有免疫调节作用，有待进一步全面研究。
