Dorshkind K, Yoshida S, Gershwin M E
Division of Biomedical Sciences, University of California, Riverside 92521-0121.
J Autoimmun. 1989 Apr;2(2):173-86. doi: 10.1016/0896-8411(89)90153-4.
The formation of B lymphocytes in young New Zealand Black (NZB) mice proceeds at an accelerated rate, resulting in a deficiency of B lineage progenitors in mice of 15 weeks of age and older. Multiple studies have indicated that intrinsic defects in B lineage cells as well as in the hemopoietic microenvironment in which they develop contribute to these cellular abnormalities. To determine whether the B-cell hyperactivity observed in young mice could be observed in a normal environment, bone marrow cells from young (4 weeks or less) NZB donors were transplanted into Severe Combined Immunodeficient (SCID) mice that have a marked deficiency of lymphocytes but an apparently normal hemopoietic microenvironment. Engraftment of donor lymphoid cells can occur without pretransplant conditioning regimens, thus minimizing the chances of transferring microenvironmental elements. Marrow from young NZB donors reconstituted surface IgM-expressing B cells and CFU-B (B-cell colony-forming unit) in the marrow of SCID mouse recipients to levels comparable to that observed with donor NZB.xid marrow. The latter mice carry the xid gene that ameliorates the defects exhibited by B lineage cells of NZB mice. Both the number of surface IgM-expressing B cells and CFU-B were higher in the spleen of SCID mice that received NZB grafts than marrow cells from donor BALB/c or NZB.xid mice. Marrow from young NZB donors also reconstituted Thy-1, L3T4 and Lyt2-expressing cells in the spleen to levels higher than observed with young NZB.xid donor cells. The transplantation of marrow from 6-month-old NZB donors made it possible to test whether B lineage cells were present in that tissue and could mediate reconstitution in the normal SCID environment. Marrow from old NZB donors did reconstitute B cells in the marrow and spleen of SCID recipients. The level of reconstitution was comparable to that mediated by young BALB/c cells and twice that of old NZB.xid donor cells. The absolute number of splenic CFU-B was also higher in recipients of old NZB marrow as compared to young BALB/c cells. Old NZB.xid donor marrow reconstituted splenic Thy-1, L3T4 and Lyt2 T cells to levels less than observed with NZB donor cells. Analysis of serum Ig in recipients of old NZB cells indicated higher levels of total IgM as compared to mice engrafted with NZB.xid cells, and anti-single stranded DNA antibodies were detected.
年轻的新西兰黑鼠（NZB）体内B淋巴细胞的形成速度加快，导致15周龄及以上的小鼠B系祖细胞缺乏。多项研究表明，B系细胞以及它们发育所处的造血微环境中的内在缺陷导致了这些细胞异常。为了确定在正常环境中是否能观察到幼鼠中出现的B细胞活性亢进，将年轻（4周龄及以下）NZB供体的骨髓细胞移植到严重联合免疫缺陷（SCID）小鼠体内，SCID小鼠淋巴细胞明显缺乏，但造血微环境明显正常。供体淋巴细胞的植入无需移植前预处理方案，从而将转移微环境成分的可能性降至最低。来自年轻NZB供体的骨髓将SCID小鼠受体骨髓中表达表面IgM的B细胞和CFU - B（B细胞集落形成单位）重建到与供体NZB.xid骨髓相当的水平。后一种小鼠携带xid基因，该基因可改善NZB小鼠B系细胞所表现出的缺陷。接受NZB移植的SCID小鼠脾脏中表达表面IgM的B细胞数量和CFU - B均高于接受供体BALB/c或NZB.xid小鼠骨髓细胞的SCID小鼠。来自年轻NZB供体的骨髓还将脾脏中表达Thy - 1、L3T4和Lyt2的细胞重建到高于年轻NZB.xid供体细胞的水平。移植6月龄NZB供体的骨髓使得能够测试该组织中是否存在B系细胞以及它们能否在正常的SCID环境中介导重建。来自老年NZB供体的骨髓确实在SCID受体的骨髓和脾脏中重建了B细胞。重建水平与年轻BALB/c细胞介导的水平相当，是老年NZB.xid供体细胞的两倍。与年轻BALB/c细胞相比，接受老年NZB骨髓的受体脾脏中CFU - B的绝对数量也更高。老年NZB.xid供体骨髓将脾脏中的Thy - 1、L3T4和Lyt2 T细胞重建到低于NZB供体细胞的水平。对接受老年NZB细胞的受体血清Ig的分析表明，与植入NZB.xid细胞的小鼠相比，总IgM水平更高，并且检测到了抗单链DNA抗体。
