Gärdby E, Kagrdic D, Kjerrulf M, Bromander A, Vajdy M, Hörnquist E, Lycke N
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Dev Immunol. 1998;6(1-2):53-60. doi: 10.1155/1998/75718.
It is thought that IgA B-cell differentiation is highly dependent on activated CD4+ T cells. In particular, cell-cell interactions in the Peyer's patches involving CD40 and/or CD80/CD86 have been implicated in germinal-center formation and IgA B-cell development. Also soluble factors, such as IL-4, IL-5, IL-6, and TGF beta may be critical for IgA B-cell differentiation in vivo. Here we report on some paradoxical findings with regard to IgA B-cell differentiation and specific mucosal immune responses that we have recently made using gene knockout mice. More specifically, we have investigated to what extent absence of CD4+ T cells, relevant cytokines, or T-cell-B-cell interactions would influence IgA B-cell differentiation in vivo. Using CD4- or IL-4-gene knockout mice or mice made transgenic for CTLA4Ig, we found that, although specific responses were impaired, total IgA production and IgA B-cell differentiation appeared to proceed normally. However, a poor correlation was found between, on the one hand, GC formation and IgA differentiation and, on the other hand, the ability to respond to T-cell-dependent soluble protein antigens in these mice. Thus, despite the various deficiencies in CD4+ T-cell functions seemingly intact IgA B-cell development was observed.
人们认为，IgA B细胞分化高度依赖于活化的CD4+ T细胞。特别是，派尔集合淋巴结中涉及CD40和/或CD80/CD86的细胞间相互作用与生发中心形成和IgA B细胞发育有关。此外，可溶性因子，如白细胞介素-4、白细胞介素-5、白细胞介素-6和转化生长因子β，可能对体内IgA B细胞分化至关重要。在此，我们报告了我们最近使用基因敲除小鼠在IgA B细胞分化和特异性黏膜免疫反应方面的一些矛盾发现。更具体地说，我们研究了CD4+ T细胞、相关细胞因子或T细胞与B细胞相互作用的缺失在多大程度上会影响体内IgA B细胞分化。使用CD4基因敲除小鼠、白细胞介素-4基因敲除小鼠或转染CTLA4Ig的转基因小鼠，我们发现，尽管特异性反应受损，但总IgA产生和IgA B细胞分化似乎仍正常进行。然而，一方面生发中心形成和IgA分化，与另一方面这些小鼠对T细胞依赖性可溶性蛋白抗原的反应能力之间，相关性较差。因此，尽管CD4+ T细胞功能存在各种缺陷，但仍观察到IgA B细胞发育似乎完好无损。
