Burdin N, Galibert L, Garrone P, Durand I, Banchereau J, Rousset F
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
J Immunol. 1996 Jun 1;156(11):4107-13.
In response to Ag encounter, B lymphocytes undergo a complex maturation process yielding phenotypically distinct subpopulations that are located in highly organized compartments of secondary lymphoid organs. This study describes the patterns of cytokine secretion of naive, memory, and germinal center (GC) human tonsillar B lymphocytes, activated either through CD40 or B cell receptor or with Staphylococcus aureus Cowan I particles. The three B cell subpopulations produced comparable levels of IL-10 and TNF-alpha, regardless of the stimulation pathway. Interestingly, activated GC B lymphocytes fail to express IL-6, as determined both at mRNA and at protein levels, whereas both naive and memory B cells can be induced to secrete IL-6. Likewise, naive B lymphocytes undergoing dual ligation of CD40 and B cell receptor fail to express IL-6, since they acquire a GC-like phenotype. IL-6 receptors are up-regulated on both ex vivo-purified GC B lymphocytes and in vitro generated GC-like B cells, following CD40 activation. Consistent with this, addition of exogenous IL-6 sustains growth of CD40-stimulated GC B lymphocytes. Taken together, these results demonstrate that loss of IL-6 secretion is a functional characteristic of human GC B lymphocytes. The swap from an autocrine to a paracrine IL-6 response may permit a better control of B cell growth and differentiation during the germinal center reaction.
在遇到抗原时，B淋巴细胞会经历一个复杂的成熟过程，产生表型不同的亚群，这些亚群位于二级淋巴器官高度有序的区域。本研究描述了未成熟、记忆和生发中心（GC）人扁桃体B淋巴细胞的细胞因子分泌模式，这些细胞通过CD40或B细胞受体或用金黄色葡萄球菌考恩I颗粒激活。无论刺激途径如何，这三种B细胞亚群产生的IL-10和TNF-α水平相当。有趣的是，经mRNA和蛋白质水平测定，活化的GC B淋巴细胞均不表达IL-6，而未成熟和记忆B细胞均可被诱导分泌IL-6。同样，经历CD40和B细胞受体双重连接的未成熟B淋巴细胞也不表达IL-6，因为它们获得了类似GC的表型。在CD40激活后，体外纯化的GC B淋巴细胞和体外产生的类似GC的B细胞上的IL-6受体均上调。与此一致的是，添加外源性IL-6可维持CD40刺激的GC B淋巴细胞的生长。综上所述，这些结果表明IL-6分泌的丧失是人类GC B淋巴细胞的一个功能特征。从自分泌IL-6反应转变为旁分泌IL-6反应可能有助于在生发中心反应期间更好地控制B细胞的生长和分化。
