Lindroth Karin, Fernández Carmen
Department of Immunology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Immunol Lett. 2007 Nov 15;113(2):70-5. doi: 10.1016/j.imlet.2007.07.018. Epub 2007 Aug 23.
Humoral responses against thymus-dependent (TD) antigens are characterized by Ig class switch, somatic hypermutations (SHM) and generation of memory. These processes are thought to occur in the specialized environment of the germinal center (GC). Some thymus-independent (TI) antigens, such as native dextran B512 (Dx) can also induce formation of GCs, but the responses do not undergo substantial affinity maturation or induction of memory. Immunization with TI Dx affects later TD responses against the same epitope, reducing Dx specific IgG1. We have studied if the different outcome of the TI- and TD-induced GC reaction is due to differences in plasma cell differentiation. The transcriptional repressor B lymphocyte-induced maturation protein, Blimp-1, was used as a marker for differentiation of plasma cells. We show that TI GCs contain Blimp-1 in early and mature GCs, in contrast to TD-induced GCs which strongly express Blimp-1 only in established GCs. Furthermore, the intensity of the Blimp-1 staining is stronger in TI GCs. In addition, we demonstrate that in TD responses after TI priming the pattern of Blimp-1 expression is a mixture of both TI and TD responses. This is novel evidence since these TD humoral responses against Dx display a TI isotype pattern.
针对胸腺依赖性（TD）抗原的体液免疫反应的特征在于Ig类别转换、体细胞超突变（SHM）和记忆细胞的产生。这些过程被认为发生在生发中心（GC）的特殊环境中。一些胸腺非依赖性（TI）抗原，如天然右旋糖酐B512（Dx），也能诱导GC的形成，但这种反应不会经历实质性的亲和力成熟或记忆细胞的诱导。用TI Dx免疫会影响随后针对相同表位的TD反应，降低Dx特异性IgG1。我们研究了TI和TD诱导的GC反应的不同结果是否归因于浆细胞分化的差异。转录抑制因子B淋巴细胞诱导成熟蛋白Blimp-1被用作浆细胞分化的标志物。我们发现，与仅在成熟GC中强烈表达Blimp-1的TD诱导的GC不同，TI GC在早期和成熟GC中都含有Blimp-1。此外，TI GC中Blimp-1染色的强度更强。此外，我们证明，在TI启动后的TD反应中，Blimp-1的表达模式是TI和TD反应的混合。这是新的证据，因为这些针对Dx的TD体液免疫反应呈现TI同种型模式。
