Selvey L A, Morse H C, June C H, Hodes R J
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1995 Jan 1;154(1):171-9.
MAIDS is a retrovirus-induced immunodeficiency syndrome in mice that has similarities to human AIDS. Because the functional defects in B cells from retroviral immunodeficiency syndromes have not been characterized in detail, we examined early and late parameters of B cell responses to IgM cross-linking in B cells from MAIDS and normal mice. Splenic B cells from mice with MAIDS have defective in vitro proliferative responses to LPS and anti-IgM-mediated stimuli, as well as to PMA plus calcium ionophore, indicating a generalized defect in proliferative response potential independent of specific receptor-mediated signaling. When early signaling parameters were analyzed in response to IgM cross-linking, it was found that calcium flux in B cells from MAIDS mice was significantly reduced; this reduction was not accounted for by quantitative differences in cell-surface IgM expression and therefore indicates a defect in early signal transduction through the IgM receptor. The tyrosine phosphorylation response to IgM cross-linking was also markedly deficient; tyrosine phosphorylation of Ig-alpha, Ig-beta, and an undefined protein of 80 kDa was detected in MAIDS B cells after anti-IgM stimulation, at levels substantially less than those observed in normal B cells. Multiple other tyrosine phosphorylation events observed in normal B cells, including phosphorylation of GTPase-activating protein, P13-kinase, and syk kinase, were not detected in MAIDS B cells in response to IgM cross-linking. The defect in tyrosine phosphorylation seemed to correlate with reduced surface IgM levels on a subpopulation of MAIDS B cells. B cells from mice expressing the MAIDS retrovirus-induced immunodeficiency thus reflect defects in early signaling through the Ag-specific IgM receptor as well as a generalized defect in proliferative responsiveness.
小鼠获得性免疫缺陷综合征（MAIDS）是一种由逆转录病毒引起的免疫缺陷综合征，与人类艾滋病有相似之处。由于逆转录病毒免疫缺陷综合征中B细胞的功能缺陷尚未得到详细表征，我们研究了MAIDS小鼠和正常小鼠B细胞对IgM交联的B细胞反应的早期和晚期参数。患有MAIDS的小鼠的脾脏B细胞对LPS、抗IgM介导的刺激以及佛波酯（PMA）加钙离子载体的体外增殖反应存在缺陷，这表明增殖反应潜力存在普遍缺陷，与特定受体介导的信号传导无关。当分析对IgM交联的早期信号参数时，发现MAIDS小鼠B细胞中的钙通量显著降低；这种降低不能用细胞表面IgM表达的定量差异来解释，因此表明通过IgM受体的早期信号转导存在缺陷。对IgM交联的酪氨酸磷酸化反应也明显不足；抗IgM刺激后，在MAIDS B细胞中检测到Ig-α、Ig-β和一种未确定的80 kDa蛋白的酪氨酸磷酸化，但水平远低于正常B细胞中观察到的水平。在正常B细胞中观察到的多种其他酪氨酸磷酸化事件，包括GTP酶激活蛋白、磷脂酰肌醇-3激酶（P13-激酶）和脾酪氨酸激酶（syk激酶）的磷酸化，在MAIDS B细胞对IgM交联的反应中未检测到。酪氨酸磷酸化的缺陷似乎与MAIDS B细胞亚群表面IgM水平的降低有关。因此，表达MAIDS逆转录病毒诱导的免疫缺陷的小鼠的B细胞反映了通过抗原特异性IgM受体的早期信号传导缺陷以及增殖反应性的普遍缺陷。
