João Cristina, Ogle Brenda M, Gay-Rabinstein Carlota, Platt Jeffrey L, Cascalho Marilia
Transplantation Biology Program, Mayo Clinic, Rochester, MN 55905, USA.
J Immunol. 2004 Apr 15;172(8):4709-16. doi: 10.4049/jimmunol.172.8.4709.
T cell diversity was once thought to depend on the interaction of T cell precursors with thymic epithelial cells. Recent evidence suggests, however, that diversity might arise through the interaction of developing T cells with other cells, the identity of which is not known. In this study we show that T cell diversity is driven by B cells and Ig. The TCR V beta diversity of thymocytes in mice that lack B cells and Ig is reduced to 6 x 10(2) from wild-type values of 1.1 x 10(8); in mice with oligoclonal B cells, the TCR V beta diversity of thymocytes is 0.01% that in wild-type mice. Adoptive transfer of diverse B cells or administration of polyclonal Ig increases thymocyte diversity in mice that lack B cells 8- and 7-fold, respectively, whereas adoptive transfer of monoclonal B cells or monoclonal Ig does not. These findings reveal a heretofore unrecognized and vital function of B cells and Ig for generation of T cell diversity and suggest a potential approach to immune reconstitution.
T细胞多样性曾被认为取决于T细胞前体与胸腺上皮细胞的相互作用。然而，最近的证据表明，多样性可能是通过发育中的T细胞与其他细胞的相互作用产生的，而这些细胞的身份尚不清楚。在本研究中，我们表明T细胞多样性是由B细胞和免疫球蛋白驱动的。缺乏B细胞和免疫球蛋白的小鼠胸腺细胞的TCR Vβ多样性从野生型的1.1×10⁸降至6×10²；在具有寡克隆B细胞的小鼠中，胸腺细胞的TCR Vβ多样性是野生型小鼠的0.01%。分别将不同的B细胞进行过继转移或给予多克隆免疫球蛋白，可使缺乏B细胞的小鼠胸腺细胞多样性增加8倍和7倍，而单克隆B细胞或单克隆免疫球蛋白的过继转移则没有这种效果。这些发现揭示了B细胞和免疫球蛋白在T细胞多样性产生方面迄今未被认识到的重要功能，并提示了一种免疫重建的潜在方法。
