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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 记忆B细胞在生殖中心产生，并通过快速分化为浆细胞而有助于体液免疫。最近关于HIV发病机制的报道表明，HIV感染者中与病毒相关的组织样记忆B细胞的过早耗竭可能导致抗体应答低下。在这里，我们已经证明了CD 21和CD 27分子在从不同组织分离的B细胞上的表达，以及它们在正常健康未感染和SIVMAC 251感染的恒河猴中的增殖速率。我们还研究了从外周血中分离的单阳性CD 27 + B细胞与其双阳性（CD 21 + CD 27+）B细胞对应物在体外有丝分裂原刺激后诱导免疫球蛋白产生中的作用。我们的研究结果表明，B细胞上的CD 27表达在不同组织中不同，并且在刺激3天后，与单阳性CD 27 + B细胞相比，双阳性CD 21 + CD 27 + B细胞能够产生增加的IgG。此外，它们的免疫球蛋白产生不依赖于提示记忆B细胞的T细胞帮助。我们还观察到，CD 21 + CD 27 + B细胞在扁桃体中增殖增加，随后是脾脏、空肠固有层、淋巴结和正常未感染恒河猴的外周血。在SIV感染后，与正常未感染的猕猴相比，所有组织中的CD 21 + CD 27+记忆B细胞的增殖显著降低。扁桃体中CD 21 + CD 27+记忆B细胞显著减少（p <0.004）。这些数据表明SIV感染可能通过抑制组织中记忆B细胞增殖而导致抗体应答缺陷。

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. Memory B cells are generated in germinal centers and contribute to humoral immunity by rapidly differentiating into plasma cells. Recent report on HIV pathogenesis suggests that the virus associated premature exhaustion of tissue-like memory B cells may lead to poor antibody responses in HIV infected individuals. Here we have demonstrated the expression of CD21 and CD27 molecules on B cells isolated from different tissues as well as their rate of proliferation in both normal healthy uninfected and SIVMAC251 infected rhesus macaques. We have also studied the role of single positive CD27+ B cells isolated from peripheral blood compared to their double positive (CD21+CD27+) B cell counterparts in inducing immunoglobulin production after in vitro mitogen stimulation. 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 3 days of stimulation. Furthermore, their immunoglobulin production is not dependent on T cell help suggestive of memory B cells. We have also observed an increased proliferation of CD21+CD27+ B cells in the tonsil followed by spleen, jejunum lamina propria, lymph node and peripheral blood from normal uninfected rhesus macaques after single BrdU inoculation. Following SIV infection the proliferation of CD21+CD27+ memory B cells dramatically decreased in all the tissues as compared to normal uninfected macaques. A significant reduction of CD21+CD27+ memory B cells was evident in tonsil (p0.004). These data suggest that SIV infection may contribute defective antibody response by inhibiting memory B cell proliferation in tissues.