The role of CD11a/CD18-CD54 interactions in human T cell-dependent B cell activation.
The role of CD11a/CD18-CD54 interactions in human T cell-dependent B cell activation.
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DOI：
10.4049/jimmunol.146.2.492
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发表时间：
1991-01
影响因子：
4.4
通讯作者：
S. Tohma;S. Hirohata;P. Lipsky
中科院分区：
文献类型：
--
作者：
S. Tohma;S. Hirohata;P. Lipsky
通过研究抗白细胞功能相关抗原1（LFA-1，CD 11 a/CD 18）和细胞间粘附分子1（ICAM-1，CD 54）的单克隆抗体对B细胞增殖和分化的影响，研究了这些决定因素在人T细胞和B细胞协同作用中的作用。在该模型系统中，针对LFA-1或ICAM-1（CD 54）的α（CD 11 a）或β（CD 18）链的mAb显著抑制B细胞应答。mAb不直接抑制B细胞功能，因为不抑制由福尔马林化金黄色葡萄球菌和IL-2诱导的T细胞非依赖性活化。此外，固定化抗CD 3刺激的CD 4 + T细胞的DNA合成和IL-2产生并未受到LFA-1或ICAM-1 mAb的抑制。尽管抗LFA-1的mAb抑制了固定化抗CD 3刺激的CD 4 + T细胞与B细胞共培养产生IL-2的增强作用，但加入外源性IL-2或丝裂原活化的T细胞上清液不能消除抗LFA-1或ICAM-1的mAb对B细胞反应的抑制作用。当mAb在培养的最初24小时内存在时，抑制作用最显著。来自一名患有白细胞粘附缺陷的儿童的固定化抗CD 3刺激的LFA-1阴性CD 4 + T细胞克隆可诱导B细胞应答，该应答可被抗LFA-1或ICAM-1的mAb抑制。这些结果表明，LFA-1和ICAM-1之间的相互作用在介导活化的CD 4 + T细胞和B细胞之间的协作中起重要作用，所述协作是诱导B细胞增殖和分化以及增强CD 4 + T细胞产生IL-2所必需的。此外，数据与T细胞-B细胞协作模型一致，其中静息B细胞上的LFA-1和活化的CD 4 + T细胞上的ICAM-1之间的相互作用在初始T细胞依赖性B细胞活化中起关键作用。
The role of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule 1 (ICAM-1, CD54) interactions in human T cell and B cell collaboration was examined by studying the effect of mAb to these determinants on B cell proliferation and differentiation stimulated by culturing resting B cells with CD4+ T cells activated with immobilized mAb to the CD3 molecular complex. In this model system, mAb to either the alpha (CD11a) or beta (CD18) chain of LFA-1 or ICAM-1 (CD54) inhibited B cell responses significantly. The mAb did not directly inhibit B cell function, inasmuch as T cell-independent activation induced by formalinized Staphylococcus aureus and IL-2 was not suppressed. Moreover, DNA synthesis and IL-2 production by immobilized anti-CD3-stimulated CD4+ T cells were not suppressed by the mAb to LFA-1 or ICAM-1. Although the mAb to LFA-1 inhibited enhancement of IL-2 production by co-culture of immobilized anti-CD3-stimulated CD4+ T cells with B cells, addition of exogenous IL-2 or supernatants of mitogen-activated T cells could not abrogate the inhibitory effects of the mAb to LFA-1 or ICAM-1 on B cell responses. Inhibition was most marked when the mAb were present during the initial 24 h in culture. Immobilized anti-CD3-stimulated LFA-1-negative CD4+ T cell clones from a child with leukocyte adhesion deficiency could induce B cell responses, which were inhibited by mAb to LFA-1 or ICAM-1. These results indicate that the interactions between LFA-1 and ICAM-1 play an important role in mediating the collaboration between activated CD4+ T cells and B cells necessary for the induction of B cell proliferation and differentiation, and for enhancement of IL-2 production by CD4+ T cells. Moreover, the data are consistent with a model of T cell-B cell collaboration in which interactions between LFA-1 on resting B cells and ICAM-1 on activated CD4+ T cells play a critical role in initial T cell-dependent B cell activation.