Schrader C E, Stavnezer J, Kikutani H, Parker D C
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655, USA.
J Immunol. 1997 Jan 1;158(1):153-62.
To investigate the role of CD40 ligand in the delivery of help to B cells, we examined the Ag-specific interaction of B cells from CD40-deficient mice with a Th2 cell line in vitro. Small resting B cells from normal mice are stimulated to synthesize DNA when they present monovalent Ag (rabbit Fab anti-Ig) to a rabbit Ig-specific Th cell line. This response, which is independent of a signal through the B cell Ag receptor (sIg), is nearly absent in B cells from CD40-deficient mice. The CD40-deficient B cells are not defective in Ag presentation because they induce T cell IL-4 synthesis as well as normal B cells. Also, CD40-deficient B cells respond to T cell help with DNA synthesis almost as well as normal B cells if an additional signal is provided through sIg. In conjunction with a sIg signal, cell contact with helper T cells induces DNA synthesis more effectively than soluble cytokines. CD40-independent T cell help can also be measured as an early increase in c-myc mRNA levels in CD40-deficient B cells presenting Ag to helper T cells, although the levels of c-myc RNA expression are lower than those in normal B cells. However, c-myc RNA induced by noncognate interaction with anti-CD3-activated T cells is completely CD40 dependent. We conclude that early growth signals from activated Th cells are received by CD40-/- B cells, but that CD40 and/or sIg signals are required for efficient induction of DNA synthesis.
为了研究CD40配体在向B细胞提供辅助作用中的作用，我们在体外检测了来自CD40缺陷小鼠的B细胞与Th2细胞系的抗原特异性相互作用。当正常小鼠的静止小B细胞将单价抗原（兔Fab抗Ig）呈递给兔Ig特异性Th细胞系时，它们会被刺激合成DNA。这种反应不依赖于通过B细胞抗原受体（sIg）的信号，在来自CD40缺陷小鼠的B细胞中几乎不存在。CD40缺陷的B细胞在抗原呈递方面没有缺陷，因为它们与正常B细胞一样能诱导T细胞合成IL-4。此外，如果通过sIg提供额外信号，CD40缺陷的B细胞对T细胞辅助的DNA合成反应几乎与正常B细胞一样好。与sIg信号一起，与辅助性T细胞的细胞接触比可溶性细胞因子更有效地诱导DNA合成。不依赖CD40的T细胞辅助作用也可以通过向辅助性T细胞呈递抗原的CD40缺陷B细胞中c-myc mRNA水平的早期升高来衡量，尽管c-myc RNA表达水平低于正常B细胞。然而，与抗CD3激活的T细胞的非同源相互作用诱导的c-myc RNA完全依赖于CD40。我们得出结论，活化的Th细胞发出的早期生长信号被CD40 - / - B细胞接收，但高效诱导DNA合成需要CD40和/或sIg信号。
