Brière F, Bridon J M, Chevet D, Souillet G, Bienvenu F, Guret C, Martinez-Valdez H, Banchereau J
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
J Clin Invest. 1994 Jul;94(1):97-104. doi: 10.1172/JCI117354.
We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete antibodies. However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell differentiation even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce IgM, IgG, and IgA, and Ig levels are further increased by SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but not IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, SAC and anti-CD40 mAb stimulate B cells to differentiate into cells secreting IgG and IgM whereas IL-10 plays a central role in inducing B cells from IgA-D patients to differentiate into IgA secreting cells.
我们之前已经表明，在由CD32转染的成纤维细胞系呈递的抗CD40单克隆抗体组成的CD40系统中培养的人B淋巴细胞会增殖，但不分泌抗体。然而，添加金黄色葡萄球菌考恩株（SAC）颗粒即使在没有外源性细胞因子的情况下也能诱导B细胞分化（CD40/SAC系统）。此外，在人IL-10存在的情况下，在CD40系统中培养的B淋巴细胞会产生IgM、IgG和IgA，并且SAC会进一步提高Ig水平。在此，我们研究了IgA缺乏症（IgA-D）患者外周血淋巴细胞分泌免疫球蛋白，特别是CD40触发后分泌IgA的能力。在CD40/SAC系统中培养的IgA-D患者的外周血单个核细胞（PBMNC）产生IgM和IgG，但不产生IgA。向培养物中添加IL-10可增强IgM和IgG的产生，并且最显著地诱导产生大量IgA。向仅通过CD40激活的IgA-D患者的PBMNC中添加IL-10会导致IgA的产生。因此，SAC和抗CD40单克隆抗体刺激B细胞分化为分泌IgG和IgM的细胞，而IL-10在诱导IgA-D患者的B细胞分化为分泌IgA的细胞中起核心作用。
