Punnonen J, de Vries J E
DNAX Research Institute, Human Immunology Department, Palo Alto, CA 94304-1104.
J Immunol. 1993 Jul 1;151(1):100-10.
In the present study, it is demonstrated that functionally mature B cells are present in human thymus early during fetal life. Interestingly, 46 +/- 7% of fetal and postnatal thymic CD19+ B cells co-expressed CD2. Adult peripheral blood or splenic B cells were CD2-, and < 5% of fetal BM or fetal splenic CD19+ cells expressed CD2, indicating that CD2 is expressed preferentially on thymic B cells. Fetal thymic CD2+ B cells have a mature phenotype, because they are CD20+, CD40+, and surface IgM+, but they lack CD34 expression. They are also functionally mature because total thymic cell populations or highly purified CD2+ thymic B cells underwent Ig isotype switching and differentiation into Ig-secreting cells in a similar fashion as conventional B cells after culturing in the presence of IL-4 and activated cloned CD4+ T cells and anti-CD40 mAb cross-linked to Fc gamma RII/CDw32 transfected into murine L cells (Fc gamma RII+/L). Engagement of CD2 on thymic B cells by LFA-3+ L cell transfectants, anti-CD2 mAb cross-linked to Fc gamma RII+/L, or a mitogenic combination of anti-CD2 mAb did not result in proliferation or Ig production under the present conditions. However, anti-CD2 mAb enhanced IL-4 dependent Ig-synthesis by thymic B cells in the presence of activated CD4+ T cells, but they were ineffective when the B cells were activated by anti-CD40 mAb, suggesting that the anti-CD2 mAb stimulated antibody production indirectly via CD4+ T cells. Similarly, IL-7 enhanced IL-4-induced Ig production in the presence of CD4+ T cells. This effect of IL-7 also appeared to be indirect because no enhancement in Ig levels was observed in cultures of purified thymic B cells. Collectively, our results indicate that functionally mature B cells are present in human thymus early during fetal life, and that thymic CD2+, CD19+, sIgM+ cells represent a subset of bona fide B cells, which can be induced to Ig isotype switching and Ig production in vitro in a similar fashion as conventional B cells.
在本研究中，已证明功能成熟的B细胞在胎儿期早期就存在于人类胸腺中。有趣的是，46±7%的胎儿和出生后胸腺CD19+B细胞共表达CD2。成人外周血或脾脏B细胞不表达CD2，且胎儿骨髓或胎儿脾脏CD19+细胞中表达CD2的细胞不到5%，这表明CD2优先在胸腺B细胞上表达。胎儿胸腺CD2+B细胞具有成熟的表型，因为它们表达CD20+、CD40+和表面IgM+，但缺乏CD34表达。它们在功能上也已成熟，因为在IL-4、活化的克隆CD4+T细胞以及与转染到鼠L细胞（FcγRII+/L）中的FcγRII/CDw32交联的抗CD40单克隆抗体存在下培养后，整个胸腺细胞群体或高度纯化的CD2+胸腺B细胞会经历Ig同种型转换并分化为分泌Ig的细胞，其方式与传统B细胞类似。LFA-3+L细胞转染体、与FcγRII+/L交联的抗CD2单克隆抗体或抗CD2单克隆抗体的促有丝分裂组合与胸腺B细胞上的CD2结合，在当前条件下不会导致增殖或Ig产生。然而，在活化的CD4+T细胞存在的情况下，抗CD2单克隆抗体增强了胸腺B细胞依赖IL-4的Ig合成，但当B细胞由抗CD40单克隆抗体激活时它们无效，这表明抗CD2单克隆抗体通过CD4+T细胞间接刺激抗体产生。同样，在CD4+T细胞存在的情况下，IL-7增强了IL-4诱导的Ig产生。IL-7的这种作用似乎也是间接的，因为在纯化的胸腺B细胞培养物中未观察到Ig水平的升高。总体而言，我们的结果表明功能成熟的B细胞在胎儿期早期就存在于人类胸腺中，并且胸腺CD2+、CD19+、sIgM+细胞代表真正B细胞的一个亚群，其在体外可被诱导进行Ig同种型转换并产生Ig，方式与传统B细胞类似。
