Pisetsky D S
Medical Service, Durham VA Hospital, North Carolina 27705.
Clin Exp Immunol. 1988 Jan;71(1):155-8.
To characterize functional abnormalities of B cells in murine autoimmunity, the effect of cyclosporine (CsA) on antibody responses of NZB and control BALB/c spleen cells was investigated in vitro. Under conditions of high cell density, both NZB and BALB/c spleen cells spontaneously produced IgM and IgM anti-DNA, although NZB responses were greater in magnitude and demonstrated at lower cell densities. In cultures at 5 x 10(6) cells/ml, CsA preferentially inhibited anti-DNA production by cells of both strains. However, to achieve similar levels of inhibition of both responses, significantly higher concentrations of CsA were required for cultures of NZB compared to BALB/c cells. These results support previous experiments indicating enhanced sensitivity to CsA as a pharmacological marker of autoantibody producing B cells. They further suggest that B cell activation in certain forms of autoimmunity may be associated with decreased sensitivity to immunosuppressive agents.
为了表征小鼠自身免疫中B细胞的功能异常,在体外研究了环孢素(CsA)对NZB和对照BALB/c脾细胞抗体反应的影响。在高细胞密度条件下,NZB和BALB/c脾细胞均自发产生IgM和IgM抗DNA,尽管NZB的反应强度更大且在较低细胞密度下即可表现出来。在5×10⁶个细胞/ml的培养物中,CsA优先抑制两品系细胞的抗DNA产生。然而,为了对两种反应实现相似的抑制水平,与BALB/c细胞相比,NZB培养物需要显著更高浓度的CsA。这些结果支持了先前的实验,表明对CsA敏感性增强是产生自身抗体的B细胞的药理学标志。它们进一步表明,某些形式的自身免疫中B细胞的激活可能与对免疫抑制剂的敏感性降低有关。