Sarfati M, Fournier S, Christoffersen M, Biron G
Hôpital Notre-Dame, University of Montreal, Canada.
Leuk Res. 1990;14(1):47-55. doi: 10.1016/0145-2126(90)90145-y.
In our previous studies, we reported that the sera from CLL patients contain 3 to 500 times more IgE-BFs (or soluble CD23) than the sera from normal individuals (Sarfati M., Bron D., Lagneaux L., Fonteyn C., Frost H. & Delespesse G. (1988) Elevation of IgE-binding factors in serum of patients with B cell-derived chronic lymphocytic leukemia. Blood 71, 94). In the present study, we have investigated some of the mechanisms accounting for this observation. We report that the density of CD23 expression per cell is significantly higher on the B-CLLs than on the control cells, although the proportion of CD23+ B cells is comparable in both groups (70-90% of CD20+ cells express CD23 antigen). We have next examined the influence of IL-4 on the CD23 expression, the proliferation and the differentiation of B-CLLs. The results indicate that IL-4 (i) increases CD23 expression and IgE-BFs production by normal and CLL B cells; (ii) does not promote B-CLLs proliferation or differentiation, neither by itself nor in costimulation with either anti-IgM or PMA; (iii) significantly potentiates PMA-induced IgM and IgE-BFs production by B-CLLs. It is further shown that anti-CD23 Mab does not interfere with B-CLLs proliferation or differentiation. It is concluded that: (i) the excessive production of IgE-BFs in CLL patients results not only from the enlarged pool of CD23+ B cells but also from an over-expression of CD23 on B-CLLs; (ii) CD23 is not constitutively expressed on B-CLLS and it is upregulated by IL-4; and (iii) by contrast to normal B cells, CD23 on B-CLLs may not be associated with the functional LMW-BCGF receptor.
在我们之前的研究中,我们报道慢性淋巴细胞白血病(CLL)患者血清中IgE结合因子(或可溶性CD23)的含量比正常个体血清中的含量高3至500倍(Sarfati M.、Bron D.、Lagneaux L.、Fonteyn C.、Frost H.和Delespesse G.(1988年)。B细胞来源的慢性淋巴细胞白血病患者血清中IgE结合因子升高。《血液》71卷,94页)。在本研究中,我们研究了导致这一观察结果的一些机制。我们报告,尽管两组中CD23+B细胞的比例相当(70 - 90%的CD20+细胞表达CD23抗原),但B - CLL细胞上每个细胞的CD23表达密度显著高于对照细胞。接下来,我们研究了白细胞介素 - 4(IL - 4)对B - CLL细胞的CD23表达、增殖和分化的影响。结果表明,IL - 4(i)增加正常和CLL B细胞的CD23表达和IgE结合因子的产生;(ii)无论是单独作用还是与抗IgM或佛波酯(PMA)共刺激,均不促进B - CLL细胞的增殖或分化;(iii)显著增强PMA诱导的B - CLL细胞产生IgM和IgE结合因子。进一步表明,抗CD23单克隆抗体不干扰B - CLL细胞的增殖或分化。得出的结论是:(i)CLL患者中IgE结合因子的过量产生不仅源于CD23+B细胞池的扩大,还源于B - CLL细胞上CD23的过度表达;(ii)CD23在B - CLL细胞上不是组成性表达,而是由IL - 4上调;(iii)与正常B细胞相比,B - CLL细胞上的CD23可能与功能性低分子量B细胞生长因子(LMW - BCGF)受体无关。