Blossom S, Chu E B, Weigle W O, Gilbert K M
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
J Immunol. 1997 Nov 1;159(9):4580-6.
Male BXSB mice, unlike female BXSB, develop a severe early onset lupus-like disease that has been linked to an intrinsic B cell defect. In investigating this B cell defect the present study showed that male, but not female, BXSB contained a higher percentage of large, activated splenic B cells that were more responsive to anti-CD40 mAb-induced proliferation. The hyperactivity of the large B cells from the male mice was also observed in the absence of anti-CD40 mAb or any other stimuli. In examining the mechanism of the B cell hyperactivity, it was found that 20% of unstimulated large B cells from male mice, unlike large B cells from female mice, expressed CD40 ligand (CD40L), a molecule normally expressed on activated CD4+ cells. The percentage of large B cells from the male BXSB that expressed CD40L was increased to 43% by stimulation with LPS. A functional role for CD40L expression on B cells was confirmed by showing that CD40-Ig blocked the spontaneous proliferation of the large B cells from male mice. In addition, the stimulatory capacity of the large B cells from the male mice was demonstrated by their ability to induce DNA synthesis in small B cells in a CD40L-dependent manner. These results demonstrated that large B cells from male BXSB expressed functionally active CD40L. It is likely that the B cell CD40L expression and increased susceptibility to CD40 signaling due to an intrinsic B cell hyperactivity promotes autoimmune disease in BXSB mice.
与雌性BXSB小鼠不同，雄性BXSB小鼠会发展出一种严重的早发性狼疮样疾病，这种疾病与内在的B细胞缺陷有关。在研究这种B细胞缺陷时，本研究表明，雄性而非雌性BXSB小鼠脾脏中含有较高比例的大型活化B细胞，这些细胞对抗CD40单克隆抗体诱导的增殖反应更强。在没有抗CD40单克隆抗体或任何其他刺激的情况下，也观察到雄性小鼠大型B细胞的活性过高。在研究B细胞活性过高的机制时，发现与雌性小鼠的大型B细胞不同，雄性小鼠20%未受刺激的大型B细胞表达CD40配体（CD40L），该分子通常在活化的CD4+细胞上表达。用脂多糖刺激后，雄性BXSB小鼠表达CD40L的大型B细胞百分比增加到43%。通过显示CD40-Ig阻断雄性小鼠大型B细胞的自发增殖，证实了B细胞上CD40L表达的功能作用。此外，雄性小鼠大型B细胞的刺激能力通过其以CD40L依赖方式诱导小型B细胞DNA合成的能力得到证明。这些结果表明，雄性BXSB小鼠的大型B细胞表达功能活跃的CD40L。由于内在的B细胞活性过高，B细胞CD40L表达以及对CD40信号的敏感性增加，可能促进了BXSB小鼠的自身免疫性疾病。
