Cawley D, Chiang B L, Naiki M, Ansari A A, Gershwin M E
Division of Rheumatology, Allergy, and Clinical Immunology, University of California, School of Medicine, Davis 95616.
J Immunol. 1993 Mar 15;150(6):2467-77.
We have isolated, from NZB.H-2bm12 mice, several autoreactive cloned T cell lines that provide help for anti-dsDNA IgG antibody production in vitro. The purpose of the work described herein was to examine the requirement for cognate help for the production of anti-DNA antibodies in vitro. Thus, the ability of cloned T cell lines or lymphokines derived from them to provide help for T-depleted spleen cells from both normal B6.H-2bm12 mice and SLE-prone NZB.H-2bm12 mice was examined. Two autoreactive cloned T cell lines were selected for detailed study. 410F T cells respond to APC from both I-Ab and I-Abm12 mice, whereas 410H T cells are restricted to I-Abm12. By using Percoll gradients, B cells from both low density and high density fractions were cultured with autoreactive cloned T cell lines or lymphokines secreted by such cloned T cell lines, and anti-DNA antibody production was determined. Lymphokines elicited IgM anti-ssDNA antibody production from cells in all Percoll fractions from both B6.H-2bm12 and NZB.H-2bm12 mice. Lymphokines did not elicit production of IgG anti-dsDNA antibody production by cells from 2-month-old B6.H-2bm12 mice. In contrast, substantial production of IgG anti-dsDNA antibody was observed for NZB.H-2bm12 cells in response to lymphokines alone. Thus, B cells from NZB.H-2bm12 mice, because of previous activation in vivo, can proceed to IgG anti-dsDNA antibody production in vitro without direct T cell interaction. When we examined direct T cell help for the IgG anti-dsDNA antibody response, we found that we could distinguish the actions of the two cloned T cell lines studied. 410F T cells provided help predominantly for cells from low density Percoll fractions whether the cells were derived from B6.H-2bm12 or NZB.H-2bm12 mice. 410H T cells were capable of providing help for cells from both the low and high density fractions, and this help accounted for more than half of the antibody production in vitro by cells from B6.H-2bm12 mice.
我们从NZB.H-2bm12小鼠中分离出了几种自身反应性克隆T细胞系，这些细胞系在体外可辅助抗双链DNA IgG抗体的产生。本文所述工作的目的是研究体外产生抗DNA抗体时对同源辅助的需求。因此，我们检测了克隆T细胞系或其分泌的淋巴因子对正常B6.H-2bm12小鼠和易患系统性红斑狼疮的NZB.H-2bm12小鼠的T细胞耗竭脾细胞提供辅助的能力。我们选择了两个自身反应性克隆T细胞系进行详细研究。410F T细胞对来自I-Ab和I-Abm12小鼠的抗原呈递细胞（APC）均有反应，而410H T细胞则受限于I-Abm12。通过使用Percoll梯度，将低密度和高密度组分中的B细胞与自身反应性克隆T细胞系或此类克隆T细胞系分泌的淋巴因子一起培养，并测定抗DNA抗体的产生。淋巴因子可诱导B6.H-2bm12和NZB.H-2bm12小鼠所有Percoll组分中的细胞产生IgM抗单链DNA抗体。淋巴因子不能诱导2月龄B6.H-2bm12小鼠的细胞产生IgG抗双链DNA抗体。相反，单独的淋巴因子可使NZB.H-2bm12细胞大量产生IgG抗双链DNA抗体。因此，由于在体内先前已被激活，NZB.H-2bm12小鼠的B细胞在体外无需直接与T细胞相互作用就能产生IgG抗双链DNA抗体。当我们检测直接T细胞对IgG抗双链DNA抗体反应的辅助作用时，发现我们可以区分所研究的两个克隆T细胞系的作用。无论细胞来自B6.H-2bm12小鼠还是NZB.H-2bm12小鼠，410F T细胞主要为低密度Percoll组分中的细胞提供辅助。410H T细胞能够为低密度和高密度组分中的细胞提供辅助，且这种辅助作用占B6.H-2bm12小鼠细胞体外抗体产生的一半以上。
