Whisler R L, Newhouse Y G, Lachman L B
J Immunol. 1985 Jul;135(1):172-9.
The present investigation was performed to determine whether the activation of human B cells by Staphylococcal protein A (SpA) in liquid and semi-solid cultures might be dependent on distinct subsets of peripheral blood mononuclear-phagocytes (M phi) defined by the expression of HLA-DR and HLA-DS determinants. Highly pure HLA-DR- M phi functioned as effectively as HLA-DR+ MO in supporting B cell liquid proliferative responses when SpA was continuously present in cultures. However, HLA-DR+ M phi were two to three times more effective than HLA-DR- M phi in promoting B cell proliferative responses when either M phi or B cells were pulsed with SpA and were then cultured without supplemental SpA. Similarly, B cell activation in semisolid cultures was crucially dependent on HLA-DR+ M phi because colony responses were reduced fivefold in the presence of M phi expressing low/intermediate HLA-DR levels compared to M phi-containing cells with high HLA-DR levels. HLA-DS- M phi isolated by two different techniques were more effective than HLA-DS+ M phi in supporting both liquid proliferative and colony responses of B cells. Flow microcytofluorometry analysis of the dual expression of HLA-DR and HLA-DS on highly pure HLA-DR- M phi and HLA-DR+ M phi revealed that both HLA-DR- and HLA-DR+ M phi expressed low levels of HLA-DS. Importantly, the expression of HLA-DS on HLA-DR- M phi was bimodal, with an HLA-DR-, DS+ subset and an HLA-DR-, DS-subset being present. Other experiments supported the conclusions that the differential abilities of the HLA-DR-, -DS-defined subsets of M phi to support B cell activation did not represent M phi suppressive effects or differences in IL 1 production. Collectively, these results indicate that B cell activation can be directly supported by M phi whose predominant phenotype is HLA-DR+, -DS-. Thus, the accessory cell pathway of B cell activation described here is distinct from the pathway known to be required for T cell responsiveness, and could serve to provide early alternative or ancillary signals for triggering B cells.
本研究旨在确定在液体和半固体培养中，葡萄球菌蛋白A（SpA）对人B细胞的激活是否可能依赖于由HLA - DR和HLA - DS决定簇表达所定义的外周血单核吞噬细胞（M phi）的不同亚群。当SpA持续存在于培养物中时，高度纯化的HLA - DR - M phi在支持B细胞液体增殖反应方面与HLA - DR + M phi一样有效。然而，当M phi或B细胞用SpA脉冲处理然后在无补充SpA的情况下培养时，HLA - DR + M phi在促进B细胞增殖反应方面比HLA - DR - M phi有效两到三倍。同样，半固体培养中的B细胞激活关键依赖于HLA - DR + M phi，因为与具有高HLA - DR水平的含M phi细胞相比，在表达低/中等HLA - DR水平的M phi存在的情况下，集落反应降低了五倍。通过两种不同技术分离的HLA - DS - M phi在支持B细胞的液体增殖和集落反应方面比HLA - DS + M phi更有效。对高度纯化的HLA - DR - M phi和HLA - DR + M phi上HLA - DR和HLA - DS的双重表达进行流式细胞荧光分析显示，HLA - DR - 和HLA - DR + M phi均表达低水平的HLA - DS。重要的是，HLA - DR - M phi上HLA - DS的表达是双峰的，存在一个HLA - DR - 、DS +亚群和一个HLA - DR - 、DS -亚群。其他实验支持以下结论：由HLA - DR - 、 - DS定义的M phi亚群在支持B细胞激活方面的差异能力并不代表M phi的抑制作用或IL - 1产生的差异。总体而言，这些结果表明，B细胞激活可由主要表型为HLA - DR + 、 - DS - 的M phi直接支持。因此，这里描述的B细胞激活的辅助细胞途径不同于已知T细胞反应性所需的途径，并且可以为触发B细胞提供早期替代或辅助信号。
