Chattha Kuldeep S, Firth Matthew A, Hodgins Douglas C, Shewen Patricia E
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Vet Immunol Immunopathol. 2010 Sep 15;137(1-2):99-108. doi: 10.1016/j.vetimm.2010.04.016. Epub 2010 May 21.
Limited active antibody responses in neonates following vaccination have been attributed to immaturity of the immune system and to the suppressive effects of maternal antibodies. The activating receptor CD21 (CR2), when co-ligated with membrane IgM (mIgM) by complement-bound antigen lowers the threshold for activation of B lymphocytes. The inhibitory receptor CD32 (FcgammaRII) when co-ligated with mIgM by antigen-antibody complexes raises the threshold for activation. Expression of these receptors, which potentially play roles in regulation of B cell responses in the presence of maternal antibodies in neonates, has been recently characterized in blood lymphocytes in neonatal calves. Little is known however about expression of these receptors in the lymphoid tissues, where immune responses are initiated. In this study, expression of CD21, mIgM and CD32 receptors by B lymphocytes was studied in a range of lymphoid tissues including spleen, lymph nodes and bone marrow from newborn and 7-week-old calves using flow cytometry. The proportion of naïve B lymphocytes in the lymphocyte gate was significantly lower in blood and spleen of newborn calves compared to 7-week-old calves. Over 90% of B lymphocytes expressed CD21 in the lymphoid tissues. In the lymph nodes and spleen, a lower proportion of mIgM(+) B lymphocytes expressed CD32 compared to blood. In addition, intensity of expression of CD32 on B cells in lymph nodes was significantly lower compared to that in blood, suggesting a lower potential for inhibitory signalling in B cells in the lymphoid microenvironment. Investigation of the CD5(+) B cell population (as an indicator of B1 B cells) suggested an increase in the proportion of IgM(+)CD5(+) cells with age in calves, in both blood and lymphoid tissue, in contrast to the situation in humans and mice. Overall, the majority of naïve B lymphocytes in lymphoid tissues in neonatal calves expressed both activating (CD21, mIgM) and inhibitory (CD32) receptors. These receptors may provide targets for novel adjuvants, to lower the threshold for activation of B cells in neonates, and enhance antibody responses.
新生儿接种疫苗后活性抗体反应有限,这归因于免疫系统不成熟以及母体抗体的抑制作用。激活受体CD21(CR2)与补体结合抗原共同连接膜IgM(mIgM)时,会降低B淋巴细胞的激活阈值。抑制受体CD32(FcγRII)与抗原 - 抗体复合物共同连接mIgM时,会提高激活阈值。这些受体可能在新生儿母体抗体存在的情况下对B细胞反应调节中发挥作用,最近已对新生小牛血液淋巴细胞中这些受体的表达进行了表征。然而,对于这些受体在启动免疫反应的淋巴组织中的表达知之甚少。在本研究中,使用流式细胞术研究了新生和7周龄小牛的一系列淋巴组织(包括脾脏、淋巴结和骨髓)中B淋巴细胞对CD21、mIgM和CD32受体的表达。与7周龄小牛相比,新生小牛血液和脾脏中淋巴细胞门内幼稚B淋巴细胞的比例显著更低。超过90%的B淋巴细胞在淋巴组织中表达CD21。在淋巴结和脾脏中,与血液相比,表达CD32的mIgM(+) B淋巴细胞比例更低。此外,淋巴结中B细胞上CD32的表达强度明显低于血液中的表达强度,这表明淋巴微环境中B细胞的抑制信号传导潜力较低。对CD5(+) B细胞群体(作为B1 B细胞的指标)的研究表明,与人类和小鼠的情况相反,小牛血液和淋巴组织中IgM(+)CD5(+)细胞的比例随年龄增加。总体而言,新生小牛淋巴组织中的大多数幼稚B淋巴细胞表达激活(CD21、mIgM)和抑制(CD32)受体。这些受体可能为新型佐剂提供靶点,以降低新生儿B细胞的激活阈值,并增强抗体反应。