Vitetta E S, Cambier J C, Ligler F S, Kettman J R, Uhr J W
J Exp Med. 1977 Dec 1;146(6):1804-8. doi: 10.1084/jem.146.6.1804.
During ontogeny IgD appears later than IgM on splenocytes of neonatal mice (1) and at a time when mice develop a markedly increased immune responsiveness (2). Based on these observations, it was suggested that IgD serves as a "triggering" isotype for induction of immune responses, whereas surface IgM functions as a tolerizing receptor (3). To test this hypothesis, the susceptibility of adult splenocytes (which are predominantly mu(+)delta(+)[4-6]) and neonatal splenocytes (which bear predominantly IgM [mup(+); 1, 4-6]) to tolerance induction were compared. The results indicate that neonatal splenic B cells responsive to thymus dependent (TD) antigens are exquisitely susceptible to tolerance induction compared with those from adult mice (7-9). However, cells from both adult and neonatal mice were highly susceptible to tolerance induction when thymus independent (TI) antigen was used as immunogen (8). These results suggest that the major precursor for the TD response is a mu(+)delta(+)-cell which appears late in ontogeny and is resistant to tolerance induction and that the mup(+)-cell is the major precursor for the TI response and is highly susceptible to tolerance induction. Other differences between responders for TI and TD antigens have been described previously (10-12). To test this concept, adult splenocytes were treated with papain under conditions in which IgD, but not five other surface molecules, was removed (13). Such treated splenocytes were shown to be markedly susceptible to tolerance induction, resembling TD responders from neonatal animals. This experiment was interpreted as indicating that IgD confers resistance to tolerance induction on mu(+)delta(+)-cells. To prove this interpretation, it is necessary to show that specific removal of IgD with anti-delta also results in increased susceptibility to tolerance induction and that treatment with anti-mu does not have a similar effect. In the present studies, we have removed surface IgM or IgD by antibody-induced capping and assessed the tolerance susceptibility of the treated cells. Our results demonstrate that removal of IgD, but no IgM, from TD responders increases their susceptibility to tolerance induction.
在个体发育过程中，新生小鼠脾细胞上的IgD出现时间晚于IgM(1)，此时小鼠的免疫反应性显著增强(2)。基于这些观察结果，有人提出IgD作为诱导免疫反应的“触发”同种型，而表面IgM作为耐受受体发挥作用(3)。为了验证这一假设，比较了成年脾细胞(主要为μ(+)δ(+)[4 - 6])和新生脾细胞(主要携带IgM [mup(+); 1, 4 - 6])对耐受诱导的敏感性。结果表明，与成年小鼠的脾B细胞相比，对胸腺依赖性(TD)抗原产生反应的新生脾B细胞对耐受诱导极为敏感(7 - 9)。然而，当使用胸腺非依赖性(TI)抗原作为免疫原时，成年和新生小鼠的细胞对耐受诱导均高度敏感(8)。这些结果表明，TD反应的主要前体细胞是μ(+)δ(+)细胞，其在个体发育后期出现且对耐受诱导具有抗性，而mup(+)细胞是TI反应的主要前体细胞且对耐受诱导高度敏感。TI和TD抗原应答者之间的其他差异先前已有描述(10 - 12)。为了验证这一概念，在仅去除IgD而不影响其他五种表面分子的条件下，用木瓜蛋白酶处理成年脾细胞(13)。结果显示，这种处理后的脾细胞对耐受诱导明显敏感，类似于新生动物的TD应答者。该实验被解释为表明IgD赋予μ(+)δ(+)细胞对耐受诱导的抗性。为了证实这一解释，有必要证明用抗δ特异性去除IgD也会导致对耐受诱导的敏感性增加，而用抗μ处理则不会产生类似效果。在本研究中，我们通过抗体诱导的封帽作用去除表面IgM或IgD，并评估处理后细胞的耐受敏感性。我们的结果表明，从TD应答者中去除IgD而非IgM会增加其对耐受诱导的敏感性。
