Grouard G, de Bouteiller O, Banchereau J, Liu Y J
Schering-Plough, Laboratory for Immunologic Research, Dardilly, France.
J Immunol. 1995 Oct 1;155(7):3345-52.
Germinal centers constitute microanatomic subunits within secondary follicles where B cells undergo somatic mutations, isotype switch and affinity selection. This allows the generation of memory B cells and plasma cells, whose Igs bind to the eliciting Ag with a high affinity. T cells and follicular dendritic cells (FDCs) are thought to play key roles in the germinal center reaction. To study effects of FDCs on B cell growth and differentiation, we have isolated FDC-lymphocyte clusters from human tonsils by enzymatic digestion and centrifugation of the resulting cell suspension through BSA gradient. Irradiated FDC-lymphocyte clusters induced moderate proliferation of autologous B cells. IL-2 was the only cytokine able to enhance B cell proliferation cocultured with FDCs. When B cells were activated by soluble anti-CD40 Ab with or without IL-2, IL-3, IL-4, IL-10 or IL-13, addition of FDCs increased B cell proliferation. In the presence of FDCs, maximal B cell proliferation was observed in anti-CD40 stimulated cultures supplemented with either IL-4 + IL-10 or IL-2 + IL-10. Cultures performed in the presence of IL-2 and IL-10 resulted in high levels of Ig production in the presence of FDCs. In conclusion, the present study demonstrates that freshly isolated human FDCs can enhance the growth and differentiation of CD40-activated B cells.
生发中心是次级滤泡内的微解剖亚单位，B细胞在此进行体细胞突变、同种型转换和亲和力选择。这使得记忆B细胞和浆细胞得以产生，其免疫球蛋白以高亲和力结合引发抗原。T细胞和滤泡树突状细胞（FDC）被认为在生发中心反应中起关键作用。为了研究FDC对B细胞生长和分化的影响，我们通过酶消化从人扁桃体中分离出FDC-淋巴细胞簇，并将所得细胞悬液通过BSA梯度离心。经辐照的FDC-淋巴细胞簇诱导自体B细胞适度增殖。IL-2是唯一能够增强与FDC共培养的B细胞增殖的细胞因子。当B细胞用可溶性抗CD40抗体激活时，无论有无IL-2、IL-3、IL-4、IL-10或IL-13，添加FDC都会增加B细胞增殖。在FDC存在的情况下，在补充有IL-4 + IL-10或IL-2 + IL-10的抗CD40刺激培养物中观察到最大的B细胞增殖。在IL-2和IL-10存在下进行的培养在FDC存在时导致高水平的Ig产生。总之，本研究表明，新鲜分离的人FDC可以增强CD40激活的B细胞的生长和分化。
