ANALYSIS OF ISOTYPE AND IDIOTYPE EXPRESSION IN XID MICE

T非依赖性（TI）B细胞应答对于产生 细菌荚膜多糖（TI-2抗原）的抗体， 在抗细菌免疫反应中起重要作用。 已经 提出这些反应由免疫球蛋白（IG）受体介导 通过多糖上的重复决定簇进行交联，某些 具有X染色体连锁遗传缺陷（xid）的小鼠品系， 产生这种抗体反应。 据报道，这些老鼠缺少一个 B细胞亚群，即LyB-5+细胞，拟定为TI B细胞所需 应答 T细胞产生的某些免疫球蛋白同位素的血清水平 xid小鼠的独立B细胞应答IgG 3和IgM相对较低， 其他基因相同的无缺陷小鼠。 相反，伊加 XID小鼠中的水平更高。 有人认为Lyb-5细胞 不太能够转换为并产生IgG 3同种型。 我们的数据 证明了第三种同种型IgG 2b在某些xid中过表达， 小鼠 我们还发现使用LPS培养系统， 转换为IgG 3和IgG 2 B，来自xid小鼠的B细胞不具有 转换或生产IgG 3的障碍，也没有 倾向于转换为IgG 2b。 因此，更有可能是低IgM 而IgG 3是由xid B细胞对环境刺激缺乏应答引起的。 通过细菌TI-2抗原刺激。 我们目前正在调查 IgG 2b和伊加表达升高的基础。 已经 先前报道，来自xid小鼠的B细胞不同于正常B细胞 免疫球蛋白V区的使用。 我们的实验室已经证明了使用B 细胞集落滤纸片杂交试验， XID和正常小鼠之间的平均相似性， 小鼠中，在xid中是明显的，但在正常B细胞中不是。 我们目前正在 研究这种现象的遗传基础。

T-independent (TI) B cell responses are critical for the production of antibodies to bacterial capsular polysaccharides (TI-2 antigens), and thus play an important role in anti-bacterial immune responses. It has been proposed that these responses are mediated by immunoglobulin (Ig) receptor cross-linking by repeating determinants on the polysaccharides, Certain strains of mice with an X chromosome linked genetic defect, xid, do not mount such antibody responses. These mice are reported to be missing a subset of B cells, the Lyb-5+ cells, proposed to be required for TI B cell responses. Serum levels of certain immunoglobulin isotopes produced by T independent B cell responses, IgG3 and IgM, are lower in xid mice relative to otherwise genetically identical non-defective mice. Conversely, IgA levels are higher in xid mice. It has been suggested that Lyb-5- cells are less able to switch to and produce the IgG3 isotype. Our data demonstrates that a third isotype, IgG2b, is over-expressed in some xid mice. We also have found using an LPS culture system that directs switching to IgG3 and IgG2b that B cells from xid mice do not have an impairment in switching to or production of IgG3, nor do they have a propensity to switch to IgG2b. Thus, it is more likely that the low IgM and IgG3 is caused by a lack of response of xid B cells to environmental stimulation by bacterial TI-2 antigens. We are currently investigating the basis for the elevated expression of IgG2b and IgA. It has been reported previously that B cells from xid mice differ from normal B cells in usage of immunoglobulin V regions. Our lab has demonstrated using a B cell colony filter disk hybridization assay that although V region usage is on the average similar between xid and normal mice, variation between mice is evident in xid but not normal B cells. We are currently investigating the genetic basis of this phenomenon.