IMPORTANCE OF ANTIGEN SPECIFIC IGA RESPONSES IN CONTROLLING SIV/SHIV INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究用多色流式细胞术对正常猕猴和SIV感染猕猴外周血、腋窝淋巴结、支气管肺泡灌洗、骨髓、脾、扁桃体和空肠固有层淋巴细胞(LPL)进行了广泛的B细胞分析。我们进一步描述了记忆B细胞群体及其在诱导抗体反应中的作用。研究了感染SIVMAC251的猕猴不同B细胞亚群的分布、频率和免疫表型与活化、增殖和成熟受体表达的关系。此外，我们检测和比较了淋巴组织中不同B细胞亚群的周转水平，以使它们的增殖与血浆病毒载量和疾病转归相关。结果表明，CD27在不同组织中的表达不同，CD21+CD27+双阳性B细胞在刺激6天后产生的免疫球蛋白较单阳性CD27+B细胞高。此外，它们的免疫球蛋白的产生不依赖于T细胞的帮助，这表明记忆B细胞。我们还观察到，在一次BrdU接种后，正常未感染恒河猴的扁桃体中CD21+CD27+B细胞的增殖增加，随后是脾、空肠、淋巴结和外周血中的LPL。SIV感染后，扁桃体中CD21+CD27+记忆B细胞明显低于正常未感染猕猴(p0.05)，而淋巴和脾组织中CD21+CD27+记忆B细胞的增殖显著增加。这些数据显示了非人类灵长类B细胞亚群的功能特性(激活)，并表明SIV感染可能通过抑制组织中记忆B细胞的增殖而在特定组织中诱导缺陷反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this study we have performed an extensive analysis of B cells obtained from peripheral blood, axillary lymph node, bronchoalveolar lavage, bone marrow, spleen, tonsil and lamina propria lymphocytes (LPL) of the jejunum from normal and SIV infected rhesus macaques by polychromatic flow cytometry. We have further characterized memory B cell population and their role in inducing antibody responses. The distribution, frequency, and immunophenotype in regards to activation, proliferation and maturation receptor expression of different B cell subsets were examined from macaques infected with SIVMAC251. Furthermore, we examined and compared levels of turnover of different B cell subsets in lymphoid tissues to correlate their proliferation with plasma viral load and disease outcome. Our findings demonstrate that CD27 expression on B cells varies in different tissues and that double positive CD21+CD27+ B cells are capable of producing increased IgG compared to single positive CD27+ B cells after 6 days of stimulation. Furthermore, their immunoglobulin production is not dependent on T cell help, suggestive of memory B cells. We also observed increased proliferation of CD21+CD27+ B cells in the tonsil followed by spleen, LPL of the jejunum, lymph node and peripheral blood from normal uninfected rhesus macaques after a single BrdU inoculation. Following SIV infection a significant reduction of CD21+CD27+ memory B cells was evident in tonsil (p0.05) compared to normal uninfected macaques whereas, the proliferation of CD21+CD27+ memory B cells dramatically increased in lymph node and spleen tissues. These data demonstrate functional qualities (activation) of nonhuman primate B cell subsets and suggest that SIV infection may induce defective responses in specific tissues, by inhibiting memory B cell proliferation in tissues.